T cell activation and immune function are regulated by the innate immune system through positive and negative costimulatory proteins. One such protein, B7-H4 (B7-homolog 4, also designated VTCN1), belongs to the B7 Immunoglobulin superfamily of ligand-lymphocyte interacting proteins. Expressed primarily on the membrane of lymphoid cells, B7-H4 is an immunoinhibitory protein that interacts with receptors on the surface of T lymphocytes, thus mediating cellular and humoral immune responses. Overexpression of the B7-H4 protein is associated with certain malignancies, including ovarian and breast cancer, as its interaction with T cells supresses tumor-associated immunity. Current research suggests that, similar to Mucin 16 (CA125), B7-H4 may be a useful biomarker for the early detection of ovarian cancer.