IGSF3, also known as V8 or EWI-3, is a 1,214 amino acid protein. Widely expressed with predominant expression in kidney, placenta and lung, IGSF3 localizes to the membrane and contains an N-terminal signal peptide, eight immunoglobulin (Ig) domains and a transmembrane segment. IGSF3 exhibits strong sequence and structural similarity to CD101 (32% identity), a leukocyte surface protein with seven Ig domains that is believed to play a role in T-cell activation. Despite the structural similarities between IGSF3 and CD101, IGSF3 is not expressed in peripheral blood lymphocytes and does not appear to participate in an immune function. Based on its subcellular localization and the presence of the eight Ig domains, IGSF3 is hypothesized to function as a surface receptor or as a cell adhesion molecule.