BST2 (CD317, Tetherin, HM1.24) is a type II transmembrane glycoprotein functioning as a major mediator of the innate immune defense against the dissemination of enveloped viruses by tethering virion on the cell surface. BST2 has an N-terminal cytoplasmic tail for endocytosis and cytoskeletal signaling, a transmembrane domain, an extracellular domain containing putative disulfide bonds and coiled coil region for forming homodimer, and a C-terminal GPI domain for membrane anchoring. Both the transmembrane domain and the GPI domain can insert either to the cell membrane or the viral envelope membrane and hold them together to prevent viral release. Some viruses encode proteins, such as HIV-1 and Vpu respectively, to act as antagonists to counteract BST2. BST2 is overexpressed in gastrointestinal cancers, breast cancer, lung cancer, and multiple myeloma. BST2 monoclonal antibody targeting myeloma or lung cancer cells induces cellular cytotoxicity and cell death (ADCC, antibody-dependent cell-mediated cytotoxicity). Thus, BST2 serves as a potential target for tumor immunotherapy.