Extracellular calcium sensing receptor: an overview of physiology, pathophysiology and clinical perspectives.

The identification and cloning of the extracellular calcium sensing receptor (CaR) has provided a new conceptual framework in which we can better understand the interactions between extracellular calcium and the many cell types which express the CaR. The role of the CaR in regulating extracellular calcium ion homeostasis has been well established, as has its role in genetically determined disorders such as Familial Hypocalciuric Hypercalcaemia (FHH). This recently acquired knowledge has incited the discovery of new compounds which function as positive allosteric modulators of the CaR (named calcimimetics) and which are under clinical investigation for potential use in primary and secondary hyperparathyroidism. Research into the properties of the CaR produced an overwhelming influx of data but key questions have remained unanswered. We summarize the currently available information about the function of the CaR, underlining the significant progress which has been made in deciphering its role in pathological disorders and in drug development.