Mediates heterophilic cell-cell adhesion which regulates the activation, differentiation and tissue retention of various T-cell subsets (By similarity). Interaction with CADM1 promotes natural killer (NK) cell cytotoxicity and IFNG/interferon-gamma secretion by CD8+ T-cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo (PubMed:15811952). Regulates CD8+ T-cell proliferation in response to T-cell receptor (TCR) activation (By similarity). Appears to be dispensable for CD8+ T-cell-mediated cytotoxicity (By similarity). Interaction with SCRIB promotes the late phase of cellular polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG, IL17 and IL22 production (By similarity). By interacting with CADM1 on CD8+ dendritic cells, regulates the retention of activated CD8+ T-cells within the draining lymph node (By similarity). Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells (By similarity). Interaction with CADM1 promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells (By similarity). Monomer (PubMed:23583034). May form homodimer (via Ig-like V-type domain) (PubMed:23583034, PubMed:23871486). Interacts (via Ig-like V-type domain) with CADM1 (via Ig-like V-type domain); the interaction competes with CRTAM homodimerization and CADM1 homodimerization (PubMed:15781451, PubMed:15811952, PubMed:23871486). Interacts (via PDZ-binding motif) with SCRIB (via PDZ domain 3); the interaction promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (By similarity). In a subset of CD4+ T-cells, colocalizes with SCRIB at the immunological synapse during the late phase of T-cell activation. In the immune system, expression is restricted to activated class-I MHC-restricted cells, including NKT and CD8 T-cells (PubMed:10811014, PubMed:15811952, PubMed:16300832). Strongly expressed in spleen, thymus, small intestine, peripheral blood leukocyte, and in Purkinje neurons in cerebellum. Expressed at much lower levels in testis, ovary, colon, lung and lymphoid tissues (PubMed:16300832). The extracellular domain is required for the regulation of IFNG and IL22 production, but is dispensable for late T-cell polarization. Belongs to the nectin family.