We have recently identified the human TSLL1 and TSLL2 genes, which are highly homologous to the human lung tumor suppressor gene, TSLC1. Loss of expression of the TSLL1 or TSLL2 in several cancers suggests that these genes could also act as tumor suppressors. Here, we report the isolation of the mouse orthologous genes, Tsll1 and Tsll2. The Tsll1 and Tsll2 cDNAs contain a single open reading frame of 1188 and 1164 bp encoding a putative immunoglobulin-like cell adhesion molecules of 396 and 388 amino acids, which display 95% and 98% identity with those of human TSLL1 and TSLL2, respectively. The Tsll1 and Tsll2 genes are both composed of nine exons and mapped on mouse chromosome 1q H2-H4 and on 7q A3-B2, respectively, both of which conserve syntenies with human chromosomes 1q and 19q. Like the human TSLL1, the mouse Tsll1 was expressed exclusively in the brain and neurogenic cells, while Tsll1 expression was lost in one of four rodent neuroblastoma cell lines. Tsll2 was expressed in the brain and several organs including the kidney and liver, whereas loss of Tsll2 expression was detected in some rodent cancer cells derived from these tissues. Furthermore, both murine TSLL1 and TSLL2 proteins were expressed on the plasma membrane, especially at the cell-cell attached site. These data, together with their strong conservation during the vertebrate evolution, suggest that TSLL1and TSLL2 could play an important role in cell-cell interaction as well as in tumor suppression.