In conclusion, our studies have identified that non-Arg15 AP2σ mutations may be associated with impaired CaSR-mediated Ca  i2+ signalling and hypercalcaemia, and that such mutations may cluster at the AP2σ–AP2α inter-subunit interface, and disrupt formation of the AP2 complex with deleterious effects on CaSR function and Ca  e2+ homeostasis. This evidence concerns the gene CASR and Hypercalcemia.