Natural killer cell protein 46 (NKp46)

Natural killer cell protein 46 (NKp46) is a cell surface activating receptor uniquely highly expressed on human and murine natural killer (NK) cells, though recent research shows limited expression in subsets of other lymphoid cells. NKp46 is a type I transmembrane protein belonging to the immunoglobulin superfamily, characterized by two extracellular C2-type Ig-like domains. The protein acts as a "natural cytotoxicity receptor" and plays a key role in triggering NK cell-mediated cytolysis of tumor cells and virally infected cells through the induction of calcium fluxes, cytokine secretion (e.g., IFN-γ, TNF-α), and immune synapse formation. While its ligands are not fully defined, blockade of NKp46 impairs anti-tumor and anti-viral responses, which is underscored by its use as a biomarker and its implication in immune surveillance. Alterations in NKp46 expression or function have been tied to cancer prognosis and immune evasion by pathogens. The gene coding for NKp46 is NCR1, located in the Leukocyte Receptor Complex on chromosome 19q13.4 in humans.

Other names

NKp46NCR1 (Natural cytotoxicity receptor 1)CD335 (cluster of differentiation 335)p46

Antibody-mediated blockade (antibodies bind NKp46, inhibit its ability to activate NK cells, reducing cytotoxicity). Antibody cross-linking (antibodies engage NKp46 and trigger activation signaling, enhancing NK cell function; used in research context).