BetaKlotho is a 1044 amino acid single-pass type III membrane protein that plays a key role in bile acid and cholesterol metabolism by suppressing transcription of CYP7A1 (cholesterol 7-alpha-hydroxylase), the rate-limiting enzyme in bile acid synthesis. Homozygous negative betaKlotho mice showed dramatically elevated bile acid synthesis and secretion, as well as a strong upregulation of CYP7A1 and CYP8B1 and resistance to gallstone formation. FGF19 and FGF21 require direct interaction with betaKlotho for activation, intracellular signaling and gene expression modulation. Both Klotho and betaKlotho consist of two internal repeats similar to family 1 glycosidases. BetaKlotho contains two glycosyl hydrolase 1 regions, however since these regions lack essential glutamic acid residues at specific and crucial locations, the domains appear to be inactive.