Alpha-Klotho as a regulator of calcium homeostasis

α -klotho was identified as a gene associated with premature aging–like phenotypes characterized by short lifespan. In mice, we found the molecular association of α-Klotho (α-Kl) and Na + ,K + -adenosine triphosphatase (Na + ,K + -ATPase) and provide evidence for an increase of abundance of Na + ,K + -ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca 2+ ] e ) rapidly induce regulated parathyroid hormone (PTH) secretion in an α-Kl- and Na + ,K + -ATPase–dependent manner. The increased Na + gradient created by Na + ,K + -ATPase activity might drive the transepithelial transport of Ca 2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of α-Kl in the regulation of calcium metabolism.