INS and osteopetrosis: Although V-ATPase is a well-known proton pump, a study of oc/oc mice, which are a osteopetrosis model with a mutation in the TCIRG1 gene encoding the a3 isoform, revealed that a3 is important for insulin production and secretion: the a3 isoform colocalizes well with insulin in pancreatic β cells, and the blood insulin level is significantly lower in oc/oc mice than in wild-type (WT) mice when the blood glucose level is high28.