Mouse Calcium Sensing Receptor (CASR) Protein

Background

Calcium Sensing Receptor (CASR) is a G-protein-coupled receptor (GPCR) that plays a central role in maintaining systemic calcium homeostasis. CASR is primarily expressed in the parathyroid glands, kidneys, and bone, where it detects minute changes in extracellular calcium levels. Activation of CASR in the parathyroid glands leads to the inhibition of parathyroid hormone (PTH) secretion, a key regulator of calcium and phosphate balance. This prevents excessive calcium resorption from bone and calcium reabsorption in the kidneys, helping to maintain optimal calcium concentrations. CASR signaling in the renal tubules enhances calcium excretion and regulates water balance, contributing to fluid and electrolyte homeostasis. Beyond calcium regulation, CASR influences processes such as bone remodeling, insulin secretion, and vascular smooth muscle tone, playing critical roles in skeletal, metabolic, and cardiovascular health. Mutations in the CASR gene are linked to disorders such as familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), conditions characterized by dysregulated calcium sensing and metabolism. CASR is also implicated in diseases like chronic kidney disease (CKD), where calcium-phosphate imbalances are common, and in cancers such as breast cancer, where CASR promotes tumor cell growth and metastasis to bones. Therapeutically, CASR modulators like calcimimetics are used to treat secondary hyperparathyroidism and hypercalcemia in conditions such as primary hyperparathyroidism. Research into CASR signaling continues to reveal its broader roles in inflammation, cell proliferation, and immune response, highlighting its importance as a potential therapeutic target for metabolic and bone disorders.