Mouse poliovirus receptor (PVR, CD155) is a type I transmembrane (TM) glycoprotein that is a member of the nectin-related family of adhesion proteins within the immunoglobulin superfamily. It binds other molecules including vitronectin, Nectin3, DNAM1, CD96, and TIGIT, but does not bind homotypically. CD155 includes a 28 aa signal sequence, a 318 aa extracellular domain (ECD) with one N-terminal V-type and two C2-type Ig-like domains, a 24 aa TM segment and a 38 aa cytoplasmic tail. Epithelial, endothelial, and many immune cells show low CD155 expression. It is up-regulated on endothelia by IFNγ, and is highly expressed on immature thymocytes, lymph node dendritic cells, and tumor cells of epithelial and neuronal origin. On migrating cells, it is concentrated at the leading edge, where it binds basement membrane vitronectin, recruits Nectin-3-expressing cells, and cooperates with PDGF and integrin αvβ3 to promote cell migration. Binding of monocyte DNAM-1 to endothelial cell CD155 promotes transendothelial migration. Enhanced CD155 expression in tumor cells contributes to loss of contact inhibition and increased migration, but also allows tumor cell recognition and killing by DNAM-1or CD96 expressing NK cells.