Ksp-cadherin is a novel kidney-specific member of the cadherin superfamily of cell adhesion molecules. We have determined the complete cDNA coding sequences of both the human and the mouse isoforms of Ksp-cadherin. The inferred amino acid sequences of the human and mouse isoforms are 79 and 75% identical to the originally described rabbit isoform of Ksp-cadherin (Thomson et al., 1995; J. Biol. Chem. 270, 17594-17601), respectively. The relative locations of cadherin-specific sequence motifs, putative N- glycosylation sites, and characteristic protein domains are entirely conserved in all three isoforms. Multiple organ Northern analyses indicate that, as in the rabbit, both the human and the mouse Ksp-cadherin transcripts appear to have distinct kidney-specific distributions. The human Ksp-cadherin gene (CDH16) maps to chromosome 16q21-proximal 16q22. The mouse Ksp-cadherin gene (Cdh16) was localized to a highly syntenic region of distal chromosome 8. Both the human and the mouse Ksp-cadherin genes were localized to previously identified clusters of cadherin gene sequences, consistent with the hypothesis that most cadherin family members arose by gene duplication from a single ancestral gene at a relatively early stage in the evolution of the mammalian genome.