CD112/Nectin-2, also known as poliovirus receptor related protein 2 (PVRL2 ), is a Ca2+ independent immunoglobulin-like cell adhesion molecule that belongs to the Nectin family. Nectins were originally identified as virus receptors and the family consists of four members, nectin-1, nectin-2 , nectin-3 and nectin-4. Nectins-1, nectin-2, and nectin-3 were named PVRL1, PVRL2, and PVRL3 and assigned as CD111, CD112, and CD113, respectively. Nectins mediate both homophilic and heterophilic interactions. They first form cis-homodimers followed by dimer formation in trans. The trans-interaction can be either homophilic or heterophilic. CD112/Nectin-2 also binds to DNAM-1/CD226 on NK cells. The interaction between CD112 and CD226 can induce NK cell and CD8+ T cell-mediated cytotoxicity and cytokine secretion. CD112/Nectin-2 also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus. CD112/Nectin-2 localizes to adherens junctions between neurons, endothelial cells, epithelial cells, and fibroblasts.