Klotho: Small Molecules and Peptides

The Klotho proteins, Klotho and Klotho beta (beta KL), are type I transmembrane glycoproteins with extracellular regions that contain two beta-glycosidase-like repeats. Klotho has both membrane-bound and soluble forms; the soluble form predominates and consists of only the first beta-glycosidase-like repeat. Klotho has beta-glucuronidase activity against select steroid beta-glucuronides, appears to regulate calcium and vitamin D levels in serum, and is associated with premature aging.

Klotho beta, a divergent structural member of the glycosidase I superfamily, is primarily expressed in the liver and pancreas, with lower expression in adipose tissue. Klotho beta mediates the interaction of FGF-15 (human FGF-19) with FGF Receptor 4 in the liver, which negatively regulates bile acid synthesis by controlling the secretion of two key bile acid synthase genes. Klotho beta is also a cofactor for the interaction of FGF-21 with FGF Receptor 1c in adipocytes. The expression pattern of Klotho beta suggests it may play a role in lipid metabolism.