ATP6V0B encodes the B subunit of the V0 domain of vacuolar H+-ATPase (V-ATPase), a proton-conducting component essential for the multisubunit enzyme complex responsible for acidifying intracellular compartments 1. As part of the membrane-integral V0 complex, ATP6V0B facilitates proton translocation across membranes, enabling lysosomal, endosomal, and Golgi acidification, which are critical for autophagy and cellular homeostasis 2. ATP6V0B expression is transcriptionally regulated by E2F1 and thyroid hormone (T3), with T3 upregulating ATP6V0B alongside other lysosomal genes to enhance autophagy and lysosomal activity 23. Clinically, ATP6V0B dysregulation is implicated in cancer pathogenesis. In bladder cancer, ATP6V0B overexpression promotes tumorigenesis by activating the PAQR4/PI3K/AKT signaling pathway, correlating with poor patient prognosis 4. ATP6V0B is also elevated in pancreatic cancer and has been identified as a circulating extracellular vesicle biomarker with diagnostic potential (AUC 0.86-0.88) for cancer detection 5. Additionally, genetic variants near ATP6V0B are associated with café-au-lait macule count in neurofibromatosis type 1, suggesting roles in melanocyte biology 6. In Alzheimer's disease, ATP6V0B expression is regulated by ceRNA networks involving lncRNAs and miRNAs, implicating dysregulated lysosomal function in neurodegeneration 7.