Complex regulation and diverse functions of alpha-klotho.

It has been understood that the α-klotho gene, first identified as an aging-related gene, is actually necessary for regulating mineral homeostasis in vertebrates. All vertebrates, including humans, actively maintain calcium and phosphate ions in bones, circulating blood, and cerebrospinal fluid. Therefore, disruptions in homeostasis cause osteoporosis, ectopic calcification, and epilepsy. Vitamin D and parathyroid hormone are well-known hormones for maintaining calcium and phosphate balance. Synthesis of vitamin D, secretion of parathyroid hormone, and absorption of calcium and phosphate ions are all finely controlled by α-Klotho-dependent machineries. However, the precise molecular mechanisms and functions of α-Klotho are still unclear. In this article, we present an overview of recent progress in α-klotho research, with a main focus on molecular aspects.