CD226, also known as DNAM-1, is a type I transmembrane protein belonging to the immunoglobulin superfamily and is widely expressed on the surface of immune cells, including T cells, natural killer (NK) cells, and B cells. It plays a crucial role in immune regulation by interacting with its ligands, CD155 and CD112. CD226 enhances immune cell adhesion, cytotoxic activity, and cytokine secretion upon activation. It is particularly important in antitumor immunity, where it competes with TIGIT and CD96 for ligand binding, thereby promoting the antitumor activity of immune cells. However, its function can be inhibited by the high-affinity binding of TIGIT in the tumor microenvironment. Additionally, CD226 is involved in modulating the function of regulatory T cells (Tregs), influencing immune tolerance and autoimmune responses.