AP2σ has a pivotal role in clathrin‐mediated endocytosis of GPCRs such as the CaSR, and to date more than 50 FHH3 patients with AP2σ mutations, which are all missense mutations involving the Arg15 residue (Arg15Cys, Arg15His and Arg15Leu), have been reported.12, 13, 14, 15, 16 Approximately 65% of FHH patients will have a CaSR mutation, 5% an AP2σ mutation, <1% a Gα11 mutation, and the remaining ∼30% of FHH patients are considered to have involvement of a genetic abnormality that remains to be identified. Here, CASR is linked to familial hypocalciuric hypercalcemia.