NCR3LG1 (B7-H6) is a cell surface ligand that triggers natural killer (NK) cell activation through binding to the NCR3 (NKp30) receptor 1. The protein functions as an immune checkpoint molecule involved in NK cell-mediated immunosurveillance, where the B7-H6-NKp30 complex activates NK cells and promotes release of tumor necrosis factor alpha and interferon gamma 1. NCR3LG1 is selectively overexpressed on tumor cells and has minimal expression in healthy tissues, except during inflammatory or microbial stimulation 1. The protein also mediates NKp30-dependent recognition and cytolysis of activated T cells by NK cells, representing a novel NK cell-dependent immune checkpoint that regulates T cell function 2. Clinically, NCR3LG1 shows significant disease relevance across multiple cancer types. High expression correlates with poor prognosis in bladder cancer, where it associates with advanced TNM staging, histological grade, and lymph node metastasis 3. In breast cancer, NCR3LG1 has been identified as a potential therapeutic target related to ferroptosis pathways 4. The protein is highly expressed in glioma, hematologic malignancies, and other tumor types, making it a promising biomarker for cancer diagnosis and prognosis, as well as a target for novel immunotherapeutic approaches 1.