CD112R gene encodes a single transmembrane protein consisting of a single extracellular IgV domain, one transmembrane domain, and a long intracellular domain which contains two tyrosine residues, one within an ITIM-like motif.? CD112R was initially named PVRIG for the homology observed between its second exon and the variable immunoglobulin domain of the polio virus receptor (PVR/CD155) and polio virus receptor-like (PVRL) genes.? CD112R is a cell surface receptor for CD112/Nectin-2 and may act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. ?Following interaction with CD112, CD112R inhibits T-cell proliferation and the disruption of interaction between CD112R and CD112 enhances T cell response, suggesting CD112R is a novel checkpoint for human T cells.? CD112R competes with CD226 for CD112 binding.? It has been shown the blockade of CD112R enhances Trastuzumab (first-line drug to treat breast cancer with high Her2 expression) triggered antitumor response by human NK cells.