Undisclosed ATP13A2 modulator / Merck (MSD) - LARVOL DELTA

Polyamine Metabolism in Brain Health and Disease. (PubMed, Neuropharmacol Ther) - "Additional strategies to reestablish metabolic equilibrium and support neuronal resilience include targeted manipulation of key enzymes, such as ornithine decarboxylase 1 (ODC1), spermidine/spermine acetyltransferase 1 (SAT1), spermine oxidase (SMOX), and spermine synthase (SMS), or restoration of lysosomal polyamine export via ATP13A2. This review synthesizes current understanding of polyamine metabolism in brain health and disease, by integrating molecular, cellular, and systems-level perspectives, and further highlights emerging therapeutic directions aimed at harnessing this pathway to mitigate neurological pathology."

Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Inflammation • Mental Retardation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • SAT1

Levodopa responsiveness in IEM: a systematic review and case series, beyond neurotransmitter defects (SSIEM 2026) - "The most common IEM belongs to the category of trafficking disorders (i.e TUBB4A, SLC18A2, CTNNB1), energy related defects (i.e SLC22A5, AFG3L2, PDHA1, WARS2, POLG1), lysosomal and autophagy disorders (i.e SPG11, WDR45, ATP13A2), and neurodegeneration with brain iron accumulation disorders, among others...This positive response, although in different degrees and not always sustained over time, together with low HVA levels in the CSF, may open a wide differential diagnosis when considering primary neurotransmitter defects. Further studies are needed to identify predictors of response and to better define underlying mechanisms."

Clinical • Review • CNS Disorders • Dystonia • Genetic Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • CTNNB1 • FTL • PDHA1

ATP13A2 Promotes Endothelial Angiogenic Phenotypes and Is Associated With Poor Prognosis in Liver Hepatocellular Carcinoma. (PubMed, Mol Carcinog) - "Functional knockdown data support an association with endothelial angiogenic phenotypes. Rescue, in vivo, and independent clinical validation remain required."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Identification of divergent organ-specific gene and protein expression signatures for mitochondrial function, inflammatory response, and proteostasis in the liver and brain in the rotenone-induced rat model of Parkinson's disease. (PubMed, Mol Biol Rep) - "Genes involved in mitophagy (Parkin (PARK2), p = 0.0039), oxidative stress response (Parkinson's disease protein (DJ-1), p = 0.0209), lysosomal function (Low-density lipoprotein receptor-related protein-1 (LRP1), p = 0.0418; ATPase cation transporting 13a2 (ATP13a2), p = 0.0308), and inflammation (Tumour necrosis factor alpha (TNF-α), p = 0.0171) were found upregulated in the brain of ROT-induced rats as compared to control rats, and were also significantly higher than in the liver (p < 0.05)...These findings demonstrate that distinct molecular alterations in the liver and brain following ROT treatment, including differences in the regulation of genes associated with mitophagy, oxidative stress, proteostasis, and inflammation. Our findings demonstrate tissue-specific molecular associations in the liver and brain within the ROT-induced PD model, providing new insights into the pathophysiology of neurodegeneration and identifying potential biomarkers and therapeutic..."

Journal • Preclinical • CNS Disorders • Dyslipidemia • Inflammation • Movement Disorders • Oncology • Parkinson's Disease • IFNG • LRP1 • PINK1 • PTEN • SNCA • TNFA

Parkinson's disease genetics across diverse ancestries: an observational genetic study of causal and risk variants with translational implications. (PubMed, Lancet Neurol) - "This large-scale, multi-ancestry genetic study offers crucial insights into the population-specific genetic architecture of Parkinson's disease. Whereas clinical trials targeting GBA1 and LRRK2 variant carriers are primarily performed in Europe and the USA, increased ancestral diversity in Parkinson's disease research will be crucial to improve diagnostic accuracy, enhance our understanding of disease mechanisms across populations, and ensure equitable application of and access to emerging genetically informed therapies."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • DCTN1 • LRRK2 • RAB32 • SNCA • VPS13C

A PARK9 iPSC-Derived Dopaminergic Neuron Model Enables Drug Screening Targeting Autophagy-Lysosome Pathway Dysfunction in Parkinson's Disease. (PubMed, J Neurochem) - "Here, we generated induced pluripotent stem cells (iPSCs) from a PARK9 patient carrying an ATP13A2 mutation and established mutation-corrected isogenic control iPSCs. Among these, paroxetine, Ro 25-6981, amisulpride, and PK11195 showed additional, compound-dependent effects on PARK9-associated phenotypes, including lysosomal acidification, CD63-positive vesicle accumulation, cytoplasmic pSer129 α-synuclein signals, and cleaved caspase-3 signals. These findings establish PARK9 iPSC-derived neurons as a useful model of lysosomal dysfunction-associated PD pathology and provide a practical screening platform for identifying candidate compounds that modulate autophagy-lysosome pathway-related cellular phenotypes."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • CASP3 • CD63 • CTSD

Genotype–Phenotype Patterns in Genetic Parkinson’s Disease in a Tertiary Center from Türkiye (EAN 2026) - "Rare variants—including ATP13A2, FBXO7, HTRA1, and GCH1—occurred as single cases and were linked to atypical or complex presentations. This cohort highlights the substantial genotypic and phenotypic diversity of PD in Türkiye. PRKN and GBA predominate, while rare variants contribute to atypical disease profiles."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • HTRA1

iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease. (PubMed, Nat Commun) - "Here, we describe iSCORE-PD, an isogenic collection of 65 genome-edited hPSC lines carrying disease-causing or high-risk variants in 11 PD-linked genes (SNCA, PRKN, PINK1, DJ1/PARK7, LRRK2, ATP13A2, FBXO7, DNAJC6, SYNJ1, VPS13C, and GBA1)...Including multiple independently derived clones per mutation can control for this random genetic drift. Our systematic approach ensures high quality of this publicly available iSCORE-PD resource, highlights the advantages of prime editing over conventional CRISPR/Cas9 methods, and establishes best practices for generating disease-modeling hPSC collections."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • SNCA • VPS13C

Genetic Variants and Clinical Characteristics of Young-Onset Parkinson's Disease in the Hakka Population of Western Fujian. (PubMed, Brain Behav) - "This study is the first to analyze the genetic spectrum and clinical characteristics of patients with YOPD in the Hakka population of western Fujian Province. Genetic testing of known pathogenic genes in patients with YOPD can facilitate more accurate diagnosis."

Journal • Ataxia • CNS Disorders • Movement Disorders • Parkinson's Disease • EIF4G1 • LRRK2 • NR4A2 • SNCA • TENM4 • UCHL1 • UQCRC1 • VPS13C

ATP13A2 promoted cell stemness, cisplatin resistance, autophagy, and cell progression of bladder cancer. (PubMed, Front Immunol) - "Bafilomycin A1 significantly inhibited cell stemness and reduced drug resistance, suppressing bladder cancer cell progression. Elevated expression of ATP13A2 promotes cell stemness, cisplatin resistance, autophagy, and cell progression in bladder cancer."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Role of Lysosomal Genes for Parkinson's Pathogenesis: Insights from Molecular Mechanism to Therapeutic Strategies. (PubMed, Curr Rev Clin Exp Pharmacol) - "To deliberates PD-related genes including GBA1, LRRK2, VPS35, PRKN, PINK1, TMEM175, ATP13A2, ATP10B, and DJ1, highlighting their contribution in lysosomal damage...Lysosomal pathways are critical contributors to PD pathogenesis and denote promising targets for intervention. Integrating mechanistic understandings with developing therapies underlines the importance of targeting lysosomal dysfunction to mitigate α-synuclein aggregation and advance PD treatment."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • ATP1B1 • CTSS • LRRK2

Multi-omics analysis of the mechanism by ATP13A2 regulates the tumor microenvironment and prognosis in hepatocellular carcinoma. (PubMed, Cancer Cell Int) - "The ATP13A2 gene is closely related to TME, and its high expression is indicative of poor prognosis. ATP13A2 has the potential to serve as a biomarker for prognosis and efficacy assessment of HCC and may offer a new therapeutic target for its treatment."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • TERC

A Pathogenic Heterozygous Mutation Affecting ATP13A2 in Parkinson's Disease (AAN 2026) - "Since that time, heterozygous mutations in ATP13A2 have been identified as a potential risk factor for Parkinson’s disease. As ATP13A2 has been shown to regulate α-synuclein metabolism, it can cause a positive skin biopsy, which can aid in diagnosis of less obvious genetic causes."

CNS Disorders • Movement Disorders • Parkinson's Disease

ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity. (PubMed, bioRxiv) - "In ATP13A2 knockout mice and human models, we find that genetic and pharmacological inhibition of SAM utilization in polyamine biosynthesis prevents astrocytic epigenetic reprogramming and promotes dopaminergic neuron survival. These findings reveal a direct link between polyamine metabolism, epigenetic dysfunction, and neurotoxic inflammation, uncovering new therapeutic opportunities in Parkinson's disease."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Genetic Landscape of Monogenic Parkinson's Disease in the African Population-A Systematic Review. (PubMed, Mov Disord) - "Monogenic PD in Africa shows allelic and locus heterogeneity with a very strong contribution of the LRRK2 p.(Gly2019Ser) founder variant in NA. Notably, in more than 98% of SSA PD patients no molecular cause was found. Next-generation sequencing-based technology could uncover novel causative variants that may be specific to these populations."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

Clinical Evaluation of Three KRS Families and Cellular Analysis of Distinct ATP13A2 Mutations Reveal Different Levels of Iron Accumulation. (PubMed, J Neurochem) - "In addition, the transient overexpression of the wild-type ATP13A2 attenuated the cell death caused by iron accumulation. This study demonstrated that different types of ATP13A2 mutations are related to varying levels of iron accumulation and provided an explanation for the inconsistent perspectives on the association of KRS with iron accumulation."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • FTL

Progress in modelling ATP13A2-linked neurodegeneration. (PubMed, NPJ Parkinsons Dis) - "Since the first clinical discovery of the Kufor-Rakeb syndrome, numerous ATP13A2-related models have emerged, leading to significant advances in understanding the physiology and pathophysiology of this protein. This review summarizes ATP13A2 structure, function, pathology, and insights gained from cellular and animal models, highlighting their value for elucidating disease mechanisms and therapeutic development across species and experimental systems, relevant to neurodegeneration research broadly."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

NEXT-GENERATION THERAPEUTIC TARGETS IN PRECLINICAL MOUSE MODELS OF PARKINSON`S DISEASE (ADPD 2026) - "A broad range of different markers, such as ATP13A2, NOD2, OGA, TMEM175, TRPML1, MAPT, was assessed on protein level in different brain regions using automated Western blotting... Before evaluating novel targets and pathways in preclinical mouse models, it is crucial to first determine whether the relevant pathways and biomarkers are indeed affected. This detailed profiling will ensure the selection of the most suitable models for robust preclinical testing."

Preclinical • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • MAPT

ENDOLYSOSOMAL ION CHANNELS AS NOVEL THERAPEUTIC TARGETS IN ALZHEIMER'S AND PARKINSON'S DISEASE (ADPD 2026) - "The models include AD-related APP, PSEN1 mutations as well as PD-related SNCA, GBA1, LRRK2, ATP13A2 mutations... Our findings propose a pharmacological strategy to restore lysosomal function and promote the clearance of amyloid-β and α-synuclein accumulation in AD and PD models, thereby paving the way for future research in neurodegeneration."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • SNCA

ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis. (PubMed, Proc Natl Acad Sci U S A) - "Macrophages from a PD patient carrying the ATP13A2 loss-of-expression L927P mutation exhibit excessive NLRP3 activation due to lysosomal-mitochondrial dysfunction. Our findings provide insight into PD pathogenesis, emphasizing genetic factor-driven dysregulated macrophage NLRP3 activation, particularly in ATP13A2 loss-of-expression mutation cases."

Journal • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • NLRP3

Opposing Roles for ATP13A2 and ATP13A3 in Breast Cancer Subtype-Specific Polyamine Homeostasis. (PubMed, Biomolecules) - "In contrast, ATP13A2 shows an opposing association with patient survival, suggesting divergent functional roles for these closely related transporters. Together, our findings demonstrate that polyamine regulation in breast cancer is highly subtype dependent and highlight the importance of molecular stratification when considering polyamine-directed therapeutic strategies in breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Pathophysiological Roles of Two Intracellular P-Type ATPases: The Cancer-Associated Na+,K+-ATPase α3 Isoform and the Parkinson's Disease-Related ATP13A2. (PubMed, Int J Mol Sci) - "Beyond its established role in polyamine transport, emerging evidence suggests that ATP13A2 can function as an H+,K+-ATPase-like transporter, contributing to proton and cation handling within the endolysosomal system. Together, these findings underscore the broader physiological and pathological significance of intracellular P-type K+-ATPases and highlight α3NaK and ATP13A2 as promising therapeutic targets in cancer metastasis and PD."

Journal • Review • CNS Disorders • Movement Disorders • Oncology • Parkinson's Disease • CTCs • SLC2A1

Development and validation of a robust UPLC-MS/MS method for the analysis of polyamines in cells, biofluids and tissues. (PubMed, J Pharm Biomed Anal) - "Loss of function (LoF) of the ATP13A2 protein, a polyamines transporter, has been linked to lysosomal and mitochondrial dysfunctions that play an important role in the early onset of Parkinson's disease (PD) and related neurodegenerative disorders...No carry-over and matrix effect are observed. The analysis of cell lysates, different biofluids (mouse plasma and mouse cerebrospinal fluid) and mouse brain tissue homogenates confirm the applicability of the developed method for the quantification of the polyamines included in the method."

Journal • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Studies on intellectual disability identify variants in established genes as well as confirm candidature of new genes. (PubMed, Sci Rep) - "We also identified four biallelic novel variants including missense, frameshift, and nonsense variants in ATP13A2, QPCTL, WDR62 and FMO4 in the affected patients from three families...Intrafamilial genetic heterogeneity underscored the difficulties of molecular characterization of ID in even small nuclear consanguineous families. This research yielded only the second family in literature with a homozygous FMO4 variant, strengthening its candidature with ID."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Psychiatry • LRIG2 • WDR62

Ten years of diagnosing neurodegeneration with intracerebral iron accumulation: feedback from a French reference laboratory. (HMGC 2026) - "Next-generation sequencing (NGS) analysis of the nine main genes implicated in NBIA (ATP13A2, CP, DCAF17, FA2H, FTL, C19orf12, PANK2, PLA2G6, WDR45) was performed on 264 patients... A molecular diagnosis of NBIA was established in 80 patients (28%), with the PANK2 gene being the most frequently implicated (37.5%). Our study identified atypical forms of NBIA, including four families with a dominant form linked to variants of the C19orf12 gene. Among these patients, two cases involved mosaic carriers, the only cases of mosaicism reported to date for this gene."

CNS Disorders • Genetic Disorders • ANK2