ATP6V0E2 encodes the e2 subunit of the V0 membrane domain of vacuolar H+-ATPase (V-ATPase), a multisubunit proton pump essential for acidifying intracellular compartments 1. As a V-ATPase component, ATP6V0E2 is critical for maintaining lysosomal pH and supporting autophagy and lysosomal degradation of oxidized lipoproteins 2. Unlike the ubiquitously expressed e1 subunit, ATP6V0E2 shows restricted tissue distribution, particularly in kidney and brain, suggesting specialized roles in these tissues 1. Functionally, ATP6V0E2 is essential for proper proton pump activity, as demonstrated by complementation studies in yeast 1. In cancer biology, ATP6V0E2 upregulation by the tyrosine kinase inhibitor anlotinib enhances lysosomal function and autophagy through mTOR-dependent mechanisms and TFEB-mediated transcription, promoting cancer cell apoptosis 3. Clinically, dysregulation of ATP6V0E2-AS1 (an antisense lncRNA) is associated with non-functioning pituitary adenomas, suggesting potential involvement in pituitary tumorigenesis 4. Conversely, suppression of ATP6V0E2 expression impairs lysosomal degradation capacity, contributing to atherosclerotic foam cell formation 2, highlighting its protective role in cardiovascular homeostasis.