Killer cell lectin-like receptor subfamily F member 2 (NKp65)

Killer cell lectin-like receptor subfamily F member 2 (KLRF2, NKp65) is a C-type lectin-like receptor encoded in the human natural killer gene complex and expressed predominantly by a subset of NK cells[1][4][6][8]. NKp65 acts as an activating receptor that recognizes keratinocyte-associated C-type lectin (KACL/CLEC2A), a ligand mainly expressed on human skin keratinocytes[2][4][9][10]. Upon ligand engagement, NKp65 induces cytotoxicity and stimulates the release of proinflammatory cytokines from NK cells, playing a key role in immune surveillance and skin immunobiology[1][2][4][6]. The NKp65–KACL receptor–ligand pair is genetically linked and forms a high-affinity interaction essential for dedicated recognition of keratinocytes. Structurally, NKp65 differs from related receptors by being monomeric and utilizing a hemi-ITAM motif for SYK-dependent signaling[2][4][8]. Disease associations center around immunodeficiency and potential roles in cancer and inflammation, but no drugs are currently available that specifically target NKp65/KLRF2[1][4].

Other names

KLRF2NKp65Killer cell lectin-like receptor subfamily F member 2Activating coreceptor NKp65Lectin-like receptor F2CLEC2 family memberKLRF2_HUMANHGNC:37646NCBI Gene: 100431172

Antibody-mediated blockade (e.g., mAb OMA1) can inhibit NKp65/KLRF2 interaction with KACL, preventing NK cell-mediated lysis of keratinocytes expressing KACL. Theoretical mechanisms for drugs would include modulation (inhibition or activation) of NKp65 to alter immune-mediated cytotoxicity.