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. a beta-D-glucuronoside + H2O = an alcohol + D-glucuronate Homodimer. Interacts with FGF23 and FGFR1. Isoform 1 shedding leads to a soluble peptide. 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. Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 239, and the second one lacks the essential Glu active site residue at position 872. N-glycosylated. Homozygosity for KL-VS allele is associated with decreased longevity and increased cardiovascular disease risk. The disease is caused by variants affecting the gene represented in this entry. Defects in KL may be a cause of chronic renal failure complications. Predominates over the membrane form in all tissues examined. Belongs to the glycosyl hydrolase 1 family. Klotho subfamily. The thread of life - Issue 65 of December 2005