Class I-restricted T cell-associated molecule (CRTAM), a member of nectin family and the immunoglobulin superfamily, is also known as cytotoxic and regulatory T-cell molecule, which is expressed by activated CD8+ and NK T cells. CRTAM is found in spleen, thymus, small intestine, peripheral blood, and surprisingly, in brain where it is highly expressed by Purkinje cells of the cerebellum. The high affinity of CRTAM/IGSF4 adhesion allows CRTAM to disrupt IGSF4 homotypic interactions (3 - 5). IGSF4 and T cell receptor co-engagement of CRTAM-expressing CD8+ cells induces increased IFN-gamma or IL-22 production (3, 4). Furthermore, a role in cancer surveillance through NK cell-mediated rejection of IGSF4-expressing tumors has been proposed.