ATP6V0C encodes the proton-conducting c-subunit of the V0 membrane complex of vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme responsible for ATP-dependent proton pumping and organellar acidification 1. This subunit is essential for maintaining intracellular pH homeostasis across endosomes, lysosomes, and the Golgi apparatus, and mediates autophagosome-lysosome fusion through interactions with SNARE proteins 2. ATP6V0C functions in xenophagy initiation by recruiting ATG16L1 to damaged vacuoles, with its Gln124 residue being critical for this process 3. Clinically, ATP6V0C variants are associated with developmental and epileptic encephalopathies, including Dravet-like syndrome, with de novo heterozygous missense variants causing neurodevelopmental abnormalities, corpus callosum hypoplasia, and seizures 145. In cancer contexts, ATP6V0C dysfunction impairs aerobic glycolysis in esophageal cancer cells through reduced pyruvate kinase M2 phosphorylation and nuclear translocation 6, while its upregulation promotes lysosomal over-acidification and pyroptosis in anaplastic thyroid cancer 7. In colorectal cancer, ATP6V0C expression is regulated by FOXA2-mediated transcription and influences autophagy-dependent tumor suppression 8.