Natural cytotoxicity triggering receptor 1 (NKp46) (NKp46)

Natural cytotoxicity triggering receptor 1 (NCR1), widely known as NKp46 or CD335, is a type I transmembrane glycoprotein and a founding member of the natural cytotoxicity receptor (NCR) family (UniProt P14778). It is constitutively and specifically expressed on all mature Natural Killer (NK) cells and a subset of innate lymphoid cells (ILCs), making it a definitive marker for these cell types across species (PubMed: 21546608). NKp46 functions as a potent activating receptor that triggers NK cell-mediated lysis of virus-infected and transformed cells upon binding to various ligands, including viral hemagglutinins and unidentified tumor cell surface molecules (PubMed: 31142852). In clinical oncology, NKp46 is being extensively explored as a therapeutic target through the development of multi-specific NK cell engagers (NKCEs). These agents, such as SAR443579, are designed to co-engage NKp46 and CD16a on NK cells alongside a tumor-associated antigen, thereby promoting highly specific and potent anti-tumor responses (Innate Pharma). Beyond its role in cancer surveillance, NKp46 has been implicated in the control of viral infections like influenza and the regulation of autoimmune processes, including the destruction of pancreatic beta cells in type 1 diabetes (PubMed: 22307616).

Other names

CD335NCR1LY94Natural killer cell p46-related proteinp46 NK-specific receptor

NK cell activation via multi-specific engagement (NK cell engagers) to redirect cytotoxicity toward tumor-associated antigens.