NKG2-D type II integral membrane protein (NKG2D) is a type II transmembrane glycoprotein which belongs to the CD94/NKG2 family. NKG2D is expressed on natural killer (NK) cells, CD8+ alpha-beta and gamma-delta T-cells. As an activating and costimulatory receptor, it involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. It provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. It stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. NKG2D participates in NK cell-mediated bone marrow graft rejection and survival of NK cells. It Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.