Klotho protein, soluble form (s-Klotho)

Soluble Klotho is a cleaved, circulating form of the membrane-bound Klotho protein—a type I transmembrane glycoprotein largely produced in the kidney, parathyroid gland, and choroid plexus. After being shed by proteases (ADAM10, ADAM17), soluble Klotho functions as a circulating endocrine factor. It primarily regulates mineral metabolism (phosphate and calcium), maintains endothelial and vascular integrity, and modulates inflammation, oxidative stress, and fibrosis in multiple organs through paracrine and endocrine effects. Although the classic (membrane) Klotho acts as a co-receptor for the hormone FGF23, soluble Klotho has both FGF23-dependent and independent actions, including direct modification of ion channel proteins and anti-inflammatory activities. Decreased soluble Klotho levels are associated with chronic kidney disease, cardiovascular complications, and aging-related disorders, making it an active area of research for biomarker development and therapeutic intervention.

Other names

Soluble klothosKlothosKlα-Klotho (soluble form)Klotho hormone

Enhances or replaces endogenous s-Klotho activity (e.g., recombinant s-Klotho); Modulates FGF23 signaling as a co-receptor (membrane-bound form), but s-Klotho has FGF23-independent roles as well; Inhibits pro-inflammatory and pro-fibrotic signaling (TGF-β, NF-κB, STAT); Regulates ion channel trafficking and activity via sialidase/glycosidase action; Acts as an endocrine factor to protect organs from injury.