CASR and Familial hypocalciuric hypercalcemia type 3: CaSR sustained signaling, which occurs in the absence of β-arrestin-1/2, was identified serendipitously while investigating how mutations in the heterotetrameric adaptor protein-2 σ-subunit (AP2σ) that regulates clathrin-mediated endocytosis17 impair CaSR signaling in patients with familial hypocalciuric hypercalcemia type-3 (FHH3).10