AP2S1 and hypercalcemia disease: Patients with naturally occurring mutations in the gene encoding the Ca2+-sensing receptor (CaSR) (1, 2), GNA11 encoding G protein subunit α 11 (Gα11) (3), or AP2S1 encoding the clathrin-associated adaptor protein-2 σ subunit 2 (AP2σ2) (4) develop familial hypocalciuric hypercalcemia (FHH), characterized by hypercalcemia and hypocalciuria and, in some cases, by inappropriately elevated levels (5).