ATP6V1C1 encodes the C1 subunit of the vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme complex responsible for proton transport and cellular acidification 1. The protein is essential for V-ATPase assembly and catalytic activity, maintaining pH homeostasis in intracellular compartments including lysosomes and autophagosomes 12. Mechanistically, ATP6V1C1 regulates lysosomal acidification and autophagic flux, with pathogenic variants causing gain-of-function effects that disrupt cellular homeostasis 1. The protein also influences cytoskeletal organization by co-localizing with F-actin and affecting filamentous actin arrangement 3. Disease relevance includes dominant mutations causing neurodevelopmental syndromes like DOORS syndrome through altered lysosomal function 1, and specific variants causing non-syndromic sensorineural hearing loss by impairing hair cell synaptic function and survival 2. Clinically, ATP6V1C1 is overexpressed in various cancers including oral squamous cell carcinoma and breast cancer, where it promotes metastasis and radiotherapy resistance 456. The gene serves as a potential therapeutic target, with natural compounds like veratramine showing anti-cancer effects through ATP6V1C1 inhibition 6. Additionally, ATP6V1C1 variants influence skull bone mineral density and cranial development 7.