CD335, also known as NKp46, is a 46kDa natural cytotoxicity receptor that belongs to the immunoglobulin superfamily, with two extracellular Ig-like domains. It is selectively expressed on resting and activated natural killer (NK) cells, a subset of T lymphocytes, and certain innate lymphoid cells (ILCs), including ILC1 and a subset of NCR+ ILC3 in the mucosa. CD335 plays a crucial role in the lysis of autologous, allogeneic, or xenogeneic cells by NK cells and is highly conserved in mammals. The receptor's expression and function are vital for maintaining immune balance and defense capabilities, and it may also be involved in other immune cell subsets, suggesting its potential as a target for new immunotherapy strategies.