ATP6V0A1 encodes the a1 subunit of the V0 domain of vacuolar H+-ATPase (V-ATPase), a multisubunit proton pump essential for acidifying intracellular compartments 1. As an integral membrane component of the V0 domain, ATP6V0A1 functions primarily in early endosome maturation and the transition from early to late phagosomes/endosomes 1. The protein is distributed across early and late phagosomes, lysosomes, and endosomal membranes, where it mediates proton transport necessary for organellar acidification 1. Beyond canonical lysosomal function, ATP6V0A1 regulates cholesterol absorption in colorectal cancer cells through RAB guanine nucleotide exchange factor 1-dependent endosome maturation, promoting 24-hydroxycholesterol production and immunosuppressive signaling 2. Additionally, ATP6V0A1 upregulation facilitates cadmium-induced ferroptosis in B cells via enhanced lysosomal acidification and ferritinophagy 3. ATP6V0A1 is downregulated in nephropathic cystinosis, contributing to tubular injury through impaired autophagosome turnover and mitochondrial dysfunction 4. Mutations in ATP6V0A1 cause developmental and epileptic encephalopathy 104 (DEE 104), characterized by refractory seizures, severe global developmental delay, and neuronal connectivity defects 5. ATP6V0A1 also regulates metabolic memory in obesity, controlling food intake and weight regain through adipocyte function 6.