Inactivation of the klotho (kl) gene in mice results in multiple disorders that resemble human aging. The mouse kl gene encodes a novel single-pass membrane protein with homology to beta-glucosidases. In this study, we have isolated a human homologue of the kl gene and determined its gene structure. The human kl gene is composed of 5 exons and ranges over 50 kb on chromosome 13q12. We have further identified two transcripts that encode a membrane or secreted protein. These transcripts arise from a single kl gene through alternative RNA splicing. Expression of the putative secreted form predominates over that of the membrane form. The present study provides fundamental information necessary for further analyses of the human kl gene and its functions.