Gorvin CM, et al. – Researchers aimed to present a novel heterozygous Gα11 germline mutation, Phe220Ser, which was associated with hypercalcemia in a family with familial hypocalciuric hypercalcemia type 2 (FHH2). The outcomes of this study display the importance of the Gα11 hydrophobic cleft region for calcium–sensing receptor (CaSR)–mediated activation of phospholipase C (PLC), and show that allosteric CaSR modulation can rectify the loss–of–function Phe220Ser mutation and ameliorate the hypercalcemia associated with FHH2.