Interestingly, the engagement of such non-canonical inhibitory molecules, which also include programmed cell death protein 1 (PD-1) and toll-il-1 receptor 8 (TIR-8), of ligands expressed on tumor cells, transmits shut down signals to NK cells that promote immune escape and deserve attention in cancer treatment [30,31,32,33,34]. The gene discussed is SIGIRR; the disease is cancer.