Klotho is a single transmembrane 130 KDa protein encoded by the Klotho gene. A secreted form of Klotho of 70 kD is a product of alternative splicing and the extracellular domain of membrane Klotho can be released into blood, thus functioning as a circulating substance to exert multiple systemic biological actions on distant organs. This cleaved extracellular domain of membrane Klotho is referred as soluble Klotho (sKl). Ming Chang Hu, et al. SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE. Adv Exp Med Biol. 2012 ; 728: 126–157. doi:10.1007/978-1-4614-0887-1_9
Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate coreceptor for the phosphatonin FGF23. The secreted form of Klotho seems to function as a humoral factor and seems to regulate multiple glycoproteins on the cell surface, including ion channels and growth factors, and potentially has been implicated in insulin/insulin-like growth factor receptor function. The extracellular domain of Klotho protein is clipped on the cell surface by ectodomain shedding via membrane-anchored proteases. This generates a secreted form of Klotho protein with a molecular mass of between 120 and 130 kDa that is detectable in body fluids, including blood, urine, and cerebrospinal fluid. Sridevi Devaraj, et al. American Journal of Clinical Pathology, 2012, 137, 479-485
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