Calcium-sensing receptor (CASR) functions as a sensor in the parathyroid and kidney to determine extracellular calcium concentration and to maintain calcium homeostasis. CASR regulates both secretion of parathyroid hormone and excretion of urinary calcium. Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia, which is also correlated with hyperparathyroidism. On the other hand, mutations that activate CASR cause autosomal dominant hypocalcemia. Hjalm et al. (2001) and Awata et al. (2001) have identified the binding of filamin-1 to the C-terminal tail of CASR, which may contribute to its localization in caveolae, link it to the actin-based cytoskeleton, and participate in CASR-mediated activation of MAPK. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804