ATP6V1A encodes the catalytic A subunit of the vacuolar H+-ATPase (V-ATPase), a multimeric proton pump essential for lysosomal acidification and cellular homeostasis 1. The protein functions as an ATP-dependent proton pump localized to lysosomal, endosomal, and Golgi membranes, where it maintains optimal pH for hydrolytic enzyme activity 23. ATP6V1A serves as a regulatory hub connecting lysosomal function to mTORC1 signaling through the Rag GTPases 4. The protein is phosphorylated by ATM kinase and regulates retrograde lysosomal transport and glucose uptake in neurons 2. Mutations in ATP6V1A cause developmental epileptic encephalopathies and lysosomal storage disorders characterized by altered pH homeostasis, progressive brain atrophy, infantile spasms, and intellectual disability 1. Disease-associated variants cluster within the nucleotide-binding domain and result in either decreased lysosomal acidification with impaired substrate clearance or pathological over-acidification 1. Fibroblasts from affected patients show electron-dense inclusions, lipid accumulation, and significantly smaller lysosomes 1. ATP6V1A expression is transcriptionally regulated by YY1 and negatively regulated by HIF-1α under hypoxia 56. The protein represents a therapeutic target for enhancing autophagy in neurodegenerative diseases 4.