The calcium-sensing receptor (CaSR) is a membrane-bound, G-protein-coupled receptor that is expressed in all tissues that regulate extracellular calcium homeostasis - the parathyroid glands, thyroidal C cells, bone, kidney, and intestine. The CaSR senses the level of calcium in the blood and acts, therefore, as the body's thermostat for calcium (or calciostat). When the level of calcium changes by even a few percent from its normal level, the CaSR senses this change and then modulates the functions of the cells expressing it so as to restore the level of blood calcium to normal. The CaSR-mediated regulation of the secretion of parathyroid hormone plays a particularly important role in calcium homeostasis, because it directly or indirectly modulates the functions of all tissues involved in regulating blood calcium.