ATP6V0E1 encodes a critical subunit of the V0 complex of vacuolar H+-ATPase (V-ATPase), which is responsible for lysosomal acidification and maintaining pH homeostasis in intracellular compartments 1. The protein functions as part of the membrane integral V0 complex that translocates protons, working in conjunction with the V1 complex that hydrolyzes ATP. ATP6V0E1 plays essential roles in autophagy-lysosomal pathway function, with its expression regulated by transcription factors including FOXA2 and PPARA 21. The gene's expression can be enhanced through ac4C mRNA modifications by NAT10, which increases translation efficiency and promotes lysosomal acidification 3. ATP6V0E1 has significant disease relevance, particularly in cancer where it acts as a tumor suppressor target - knockdown of ATP6V0E1 mimics tumor suppressive effects in pancreatic ductal adenocarcinoma cells 4. The protein is also implicated in esophageal cancer metastasis through enhanced lysosomal degradation of E-cadherin 3. Additionally, ATP6V0E1 serves as a biomarker component in rheumatoid arthritis scoring systems and is associated with photoreceptor dysfunction in inherited retinal diseases 56. These findings establish ATP6V0E1 as a crucial regulator of cellular pH homeostasis with broad implications for disease pathogenesis and potential therapeutic targeting.