May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).
The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Subcellular locations: Cell membrane, Apical cell membrane
Isoform 1 shedding leads to a soluble peptide.
Subcellular locations: Secreted
Subcellular locations: Secreted
Present in cortical renal tubules (at protein level). Soluble peptide is present in serum and cerebrospinal fluid. Expressed in kidney, placenta, small intestine and prostate. Down-regulated in renal cell carcinomas, hepatocellular carcinomas, and in chronic renal failure kidney.