KLRD1 (CD94) is a killer cell lectin-like receptor that functions primarily as an inhibitory receptor on natural killer (NK) cells and CD8+ T cells, regulating immune surveillance through recognition of HLA-E and MHC class I molecules 1. Upon ligand binding, KLRD1 recruits tyrosine phosphatases via ITIM sequences, suppressing NK cell cytotoxicity and cytokine production 1. During SARS-CoV-2 infection, KLRD1 engagement with HLA-E presenting viral peptides on lung epithelial cells induces NK cell and CD8+ T cell exhaustion, dampening antiviral immunity 2. KLRD1 expression is upregulated following inactivated SARS-CoV-2 vaccination, supporting adaptive immune responses 3, and appears on activated bystander CD8+ T cells in CAR T-cell therapy contexts, enabling TCR-independent cytotoxic activity 4. KLRD1-expressing cytotoxic innate lymphoid cells are enriched in inflamed mesenteric lymph nodes of inflammatory bowel disease patients, contributing to chr12 inflammation 5. Clinically, anti-CD94 monoclonal antibodies effectively deplete NK cells and reduce lung injury in transplantation models 6, while KLRD1 serves as a biomarker for coronary atherosclerosis progression and myocardial infarction risk, reflecting its role in immune-mediated cardiovascular inflammation 78.