The discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis.

1The traditional view of calcium homeostasis is that it is maintained by two essential reactions. First, changes in extracellular Ca2+ are sensed in several distinct cell types, stimulating the secretion of parathyroid hormone (PTH), 1,25(OH)(2) D and calcitonin in response to the body's requirement. Second, these calcitropic hormones then act on the calcium-translocating cells of the kidney, bone, and intestine to restore calcium balance. Recent progress indicates that alpha-Klotho and fibroblast growth factor (FGF) 23 are key players that integrate the multi-step regulatory system of calcium homeostasis that rapidly adjusts the extracellular calcium concentration and continuously maintains its concentration within a narrow physiological range. alpha-Klotho and FGF23 are also found to be major players in the regulatory system of phosphate homeostasis. Here, the demonstration of the molecular functions of alpha-Klotho and FGF23 has recently given new insight into the field of calcium and phosphate homeostasis.