ULBP1 (UL16 binding protein 1) is a stress-induced ligand that activates the NKG2D receptor on natural killer and cytotoxic T cells, mediating immune surveillance of abnormal cells 1. As a cell surface protein upregulated on virus-infected and malignant cells, ULBP1 recognition by NKG2D promotes NK cell cytotoxicity and interferon-γ production 23. ULBP1 expression is regulated through multiple mechanisms: proteasome inhibitors selectively upregulate ULBP1 transcription independent of ATM/ATR DNA damage pathways 4, while the transcription factor FOXM1 epigenetically silences ULBP1 by suppressing STING-mediated signaling, creating an immunosuppressive tumor microenvironment 5. Clinically, elevated serum ULBP1 (>2000 pg/ml) predicts poor survival in hepatocellular carcinoma patients independent of disease staging, making it a potential prognostic biomarker 6. HCV infection induces hepatocyte ULBP1 expression, triggering NK cell-mediated immune responses 3. ULBP1 represents a therapeutic target for NKG2D-based cancer immunotherapies, including CAR-T/NK cell approaches and bispecific antibodies 7. Additionally, ULBP1 knockout in genetically modified donor pigs shows promise for reducing xenograft rejection in transplantation 8.