The extracellular Ca(2+)-sensing receptor (CaR) links changes in the concentration of extracellular Ca(2+) to changes in cell function. For cells involved in the control of systemic Ca(2+) concentration, this provides an efficient receptor-mediated mechanism to rapidly counteract slight fluctuations in the circulating concentration of Ca(2+). However, all cells that express the CaR are not necessarily involved in Ca(2+) homeostasis. The recent localisation of CaR expression on a variety of cell types more usually associated with non-Ca(2+)-homeostatic endocrine function may have serious repercussions for the interpretation of data in those systems which routinely culture cells under standard hypercalcaemic conditions. This short commentary considers the literature surrounding the identification of the CaR and the potential effects of its localisation on endocrine cells not directly involved in the control of systemic Ca(2+ )homeostasis.

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