Metabolically, Tcirg1 mutations disrupt gastric parietal cell V-ATPase function, impairing calcium absorption, inducing hypocalcemia, and stimulating PTH secretion—altering insulin sensitivity, glucose metabolism (Sobacchi et al., 2013), and 1,25-dihydroxyvitamin D3 levels, potentially disrupting chondrocyte energy metabolism and accelerating OA. Here, INS is linked to Hypocalcemia.