ATP6V1F encodes a V1 subunit of vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme complex responsible for acidifying intracellular compartments and maintaining organellar pH 1. As a constituent of the V1 domain, ATP6V1F couples ATP hydrolysis to proton translocation across membranes, enabling critical cellular processes including zymogen activation, receptor-mediated endocytosis, protein sorting, and lysosomal-autophagosome fusion 2. The gene is also targeted to plasma membranes in certain cell types for extracellular acidification. Disease relevance spans multiple malignancies. ATP6V1F is upregulated in hepatocellular carcinoma, correlating with poor prognosis and immune checkpoint expression; its overexpression promotes HCC cell migration, invasion, and inhibits apoptosis 2. In kidney renal clear cell carcinoma, lower ATP6V1F expression associates with advanced cancer stages and shorter overall survival 3. ATP6V1F participates in colorectal cancer progression through lncRNA-mediated ceRNA mechanisms, particularly in rectal cancer metastasis 4. Additionally, dysregulation appears implicated in early Alzheimer's disease pathogenesis via miRNA-mediated regulatory networks 5. Beyond oncology, ATP6V1F dysfunction contributes to arsenic-induced renal injury through altered oxidative phosphorylation pathways 6, and altered expression occurs in H. pylori-associated chr7 atrophic gastritis, suggesting mitochondrial metabolic dysfunction in host-pathogen interactions 7. These findings position ATP6V1F as a biomarker for disease prognosis and potential therapeutic target across multiple pathological contexts.