Mouse DNAX accessory molecule-1(DNAM-1) is a type I transmembrane glycoprotein that belongs to the immunoglobulin superfamily. As an activating receptor, it interacts with the ligands CD155 and CD112, and activates natural killer (NK) cells via its immu-noreceptor tyrosine-based activatory motif (ITAM). Mature mouse DNAM-1 has extracellular domain (ECD) that contains two Ig-like C2-set domains, and possesses a cytoplasmic region that contains motifs for binding PDZ domains. DNAM-1 is expressed on several lymphoid and myeloid cell types and interacts with CD155/PVR and Nectin-2/CD112. Ligation of DNAM-1 promotes the activation of NK cells, CD8+ T cells, and mast cells, induces dendritic cell maturation, initiates megakaryocyte and activated platelet adhesion to vascular endothelial cells, and stimulates monocyte extravasation? Conversely, it inhibits the formation of osteoclasts. Platelet-endothelium interactions that are mediated by DNAM-1 enable the metastasis of tumor cells to the lung.