The natural cytotoxic receptor (NCR) family consists of NCR1 (NKp46/CD335), NCR2 (NKp44/CD336), and NCR3 (NKp30/CD337). They are type I transmembrane proteins belonging to the immunoglobulin (Ig) superfamily. Various pathogen-derived and host-encoded molecules have been identified as ligands for NCR. They were initially discovered through their ability to induce cytotoxicity of natural killer (NK) cells against tumor cells in vitro, and animal models have shown that NCR plays a role in tumor surveillance, viral infection, and pregnancy in vivo. NCR1/NKp46 is regarded as a universal marker of NK cells, and recent studies have found that it is also expressed by other cells, such as the first group of natural lymphocytes (ILC1), a subgroup of the third group of ILC (NCR + ILC3), and γδ T cells. NCR1/NKp46 is also expressed in some malignant NK cells, natural killer T (NKT) cells, and T-cell lymphomas, and is considered a diagnostic marker and therapeutic target for them. The cross-linking of NCR1/NKp46 can activate NK cells, and this has been studied as a promising therapeutic approach.
