ICOS ligand (ICOSLG, ICOSL or GL50) is a protein that in humans is encoded by the ICOSLG gene located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275). ICOSLG is glycosylated transmembrane structure, which is classified as a member of the B7 family due to the significant homology with B7 family members. The B7/CD28 superfamily provides both positive and negative co-signals to immunocytes in immune responses. The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses. ICOSLG delivers a potent co-stimulatory signal to T cells when engaged by ICOS, resulting in T cell activation and proliferation. The existence of ICOS/ICOSLG signal in vivo is closely associated with many mouse autoimmune disease models. Conversely, the absence of ICOS/ICOSLG signal may be a good way to relieve autoimmune disease. In view of its critical function in regulating immunohomeostasis, ICOS signaling has aroused great attention in immunodiagnosis and therapy. The ICOS/ICOSLG axis has been shown to promote either antitumor T cell responses (when activated in Th1 and other Teff) or protumor responses when triggered in Tregs. Therefore, both agonistic and antagonistic monoclonal antibodies (mAbs) targeting this pathway are being investigated for cancer immunotherapy.