However, studies of patients with familial hypocalciuric hypercalcemia type-3 (FHH3), an autosomal dominant calcitropic disorder that is due to mutations of the σ subunit of the heterotetrameric adaptor protein-2 (AP2σ), which has a critical role in clathrin-mediated endocytosis (Nesbit et al., 2013b), have reported that FHH3-associated AP2σ mutations result in increased expression of the CaSR at the PM, which is paradoxically associated with reduced CaSR signaling via Gαq/11 (Nesbit et al., 2013a). Here, CASR is linked to Familial hypocalciuric hypercalcemia type 3.