Immunoglobulin superfamily member 8 (IGSF8), also known as CD316, is a protein encoded by the IGSF8 gene in humans. It is an innate immune checkpoint that inhibits the cytotoxic activity of natural killer (NK) cells by binding to the Killer Ig-like Receptor KIR3DL2. IGSF8 is a member of the EWI subfamily of the immunoglobulin protein superfamily, containing a single transmembrane domain, an EWI motif, and a variable number of immunoglobulin domains. It interacts with tetraspanins CD81 and CD9, regulating their roles in various cellular functions, including cell migration and viral infection. IGSF8 may also function as a tumor suppressor by inhibiting the proliferation of certain cancers.