ATP6V1G1 encodes the G1 subunit of the vacuolar H+-ATPase (V-ATPase) V1 complex, which is essential for acidifying intracellular compartments including lysosomes, autophagosomes, and late endosomes 1. The protein plays a critical role in autophagy by maintaining proper autophagosome acidification, as demonstrated by studies showing that UBQLN2 mutations in ALS/FTD impair autophagy through reduced ATP6V1G1 expression and V-ATPase activity 2. ATP6V1G1 is involved in lysosomal protein degradation, with its dysfunction leading to α-synuclein accumulation in Parkinson's disease models 3. The protein also regulates late endosomal pH and Rab7 activation through interactions with RILP, influencing endosomal trafficking and mannose-6-phosphate receptor recycling 1. In systemic lupus erythematosus, ATP6V1G1 expression is regulated by the m6A demethylase FTO and affects age-associated B cell differentiation through lysosomal autophagy modulation 4. Genome-wide association studies have identified ATP6V1G1 as a pleiotropic locus associated with both bone mineral density and age at menarche, suggesting broader physiological roles 5. The protein's dysfunction has been implicated in multiple diseases including neurodegenerative disorders, autoimmune diseases, and metabolic bone disease.