Human PVRIG (poliovirus receptor related immunoglobulin domain-containing protein) is an approximately 34 kDa single transmembrane protein in the poliovirus receptor-like protein (PVR) family. PVRIG (poliovirus named receptor-related immunoglobulin domain-containing), also known as CD112R, is a novel member of the PVR-like co-signaling network. The human CD112R intracellular domain comprises two tyrosine residues, one of which is part of an ITIM-like motif and a potential site for phosphatases. In humans, CD112R is expressed on T cells (predominantly CD8+ T cells) and natural killer (NK) cells, but not on B cells, monocytes or neutrophils. PVRIG binds to a single ligand, poliovirus receptor-related 2 (PVRL2, also known as CD112 or Nectin-2), and exerts an inhibitory effect on cytotoxic lymphocyte activity, likely via an ITIM-like motif in its intracellular domain. CD112R transduces signals by recruiting tyrosine phosphatases. Additionally, CD112R potentially represents a new coinhibitory receptor that suppresses T cell receptor-mediated NFAT activation.