IGSF8 (Immunoglobulin superfamily member 8) is a member the EWI subfamily of the immunoglobulin protein superfamily, also known as EWI-2, KCT-4, LIR-D1, and PGRL. It interacts with the tetraspanins CD81 and CD9 and may regulate their role in certain cellular functions including cell migration and viral infection. IGSF8 suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. It may also play a role on integrin-dependent morphology and motility functions, and may participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain. Recent research indicates that IGSF8 is highly expressed on malignant cells with antigen presentation defects, and it interacts with NK receptors to suppress NK cell cytotoxicity.