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The normal total plasma (or serum) calcium concentration is 8.5–10.5 mg/dL (2.1–2.6 mmol/L). Ionized calcium (normal: 4.6–5.3 mg/dL [1.16–1.31 mmol/L]) is the physiologically active portion and is necessary for muscle contraction and nerve function. In most situations, measuring total calcium concentration is sufficient since changes mirror that seen in ionized calcium concentration; exceptions include patients with hypoalbuminemia and certain acid-base disorders. Calcium homeostasis is primarily maintained by parathyroid hormone (PTH) and calcitriol (1,25-dihydroxyvitamin D). Calcium also autoregulates by binding to calcium sensing receptors (CaSR) in the parathyroid gland to reduce PTH secretion and in the kidney to enhance calcium excretion. Functional defects in this protein are associated with diseases of abnormal calcium metabolism, such as familial hypocalcemia and familial hypocalciuric hypercalcemia (eTable 21–1).