We have recently identified a novel gene, termedklotho,that is involved in the suppression of several aging phenotypes. The gene encodes a membrane protein that shares sequence similarity with the β-glucosidases of bacteria and plants. In this study, we isolated ratklothocDNA and examined its tissue distribution in rats. The deduced amino acid sequence of rat Klotho protein was 1014 amino acids in length and 94 and 85% homologous to those of mouse and human Klotho proteins, respectively. Northern blot analysis using the ratklothocDNA probe identified a single transcript of 5.2 kb in size expressed predominantly in the kidney, while RT-PCR detected low levels of expression also in the brain, lung, intestine, and ovaries. During development,klothoexpression in the kidney was markedly augmented after birth. Chromosomal localization of ratklothowas mapped to 12q12. Northern blot analysis showed that expression ofklothowas markedly decreased by lipopolysaccharide (LPS)in vivo,suggesting that expression ofklothois affected by acute inflammatory stress. The present study leads to a better understanding of the physiologic and pathophysiologic roles of Klotho.