soluble Klotho

Soluble Klotho (sKlotho) is the circulating, shed extracellular domain of the transmembrane α-Klotho protein, which is primarily expressed in the kidneys and choroid plexus. It is generated through proteolytic cleavage of membrane-bound α-Klotho by secretases (such as ADAM10 and ADAM17) or via alternative splicing of the Klotho gene. Soluble Klotho acts as an endocrine and paracrine hormone with pleiotropic cytoprotective, anti-inflammatory, anti-oxidative, and anti-fibrotic effects. It plays a critical role in the regulation of mineral metabolism, calcium and phosphate homeostasis, and vascular health. In preclinical models, exogenous administration of recombinant soluble Klotho has shown therapeutic potential in chronic kidney disease (CKD), diabetic kidney disease (DKD), cardiovascular diseases, and neurodegenerative disorders. However, as of 2026, it is primarily utilized as a research reagent, with therapeutic candidates (such as recombinant proteins and gene therapies) remaining in preclinical development.

Other names

s-KLsKlothosecreted Klothosoluble alpha-Klothosoluble α-Klotho