Extracellular calcium-sensing receptor (CaSR) (CaSR)

The extracellular calcium-sensing receptor (CaSR) is a Class C G protein-coupled receptor that serves as the primary regulator of systemic calcium homeostasis (UniProt P41180). It is predominantly expressed in the parathyroid glands and the kidneys, where it monitors minute changes in extracellular ionized calcium concentrations (StatPearls: Physiology, Calcium-Sensing Receptor). Upon activation by high calcium levels, the receptor initiates signaling pathways that inhibit the synthesis and secretion of parathyroid hormone (PTH) and increase renal calcium excretion (NCBI Gene: 846). Conversely, a decrease in calcium levels reduces receptor activity, leading to increased PTH secretion to restore calcium balance via bone resorption and renal reabsorption. Mutations in the CASR gene are associated with clinical disorders such as familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia (PubMed: 29073318). In clinical practice, CaSR is a major therapeutic target for secondary hyperparathyroidism in patients with chronic kidney disease and for parathyroid carcinoma. Drugs like cinacalcet and etelcalcetide act as calcimimetics, which are positive allosteric modulators that increase the receptor's sensitivity to calcium, thereby effectively lowering PTH levels (FDA: Sensipar Label).

Other names

CASRCalcium-sensing receptorCaRG-protein coupled receptor family C group 2 member APCAR1Parathyroid cell calcium-sensing receptor

Positive allosteric modulation of the receptor to increase sensitivity to extracellular calcium, thereby inhibiting parathyroid hormone secretion.