Aging and aging related disorders are still poorly understood, but there have been a number of advances in recent years, including discovery of the klotho gene, inactivation of which produces a range of phenotypes resembling those of human aging. This review describes the discovery of the klotho gene in mice and sequencing of the cDNA, which predicted a 1014 amino acid sequence corresponding to a type-I membrane protein. The human homolog (1012 amino acid residues, with 86% homology to the mouse protein) was identified, and the human Klotho protein was characterized as a member of the beta-glucosidase family. The human klotho gene was mapped to 13q12. Possible mechanisms of the pleiotropic actions of the klotho gene are discussed. This work may ultimately lead to an understanding of at least some of the mechanisms of human aging at the molecular level.