UL16-binding protein 1 (ULBP1)

UL16-binding protein 1 (ULBP1) is a member of the NKG2D ligand family, part of a unique subset of MHC class I-related molecules that are upregulated in response to cellular stress, transformation, or infection. ULBP1 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein lacking conventional peptide-binding and β2-microglobulin interaction. Its primary role is to bind the activating immunoreceptor NKG2D on natural killer (NK) cells, CD8+ T cells, and γδ T cells, triggering immune-mediated cytotoxicity against cells displaying abnormal ULBP1 expression. ULBP1 is overexpressed in various hematologic and solid tumors, making it a promising immunotherapeutic target in cancer, particularly in novel CAR-T and antibody-based therapies. Its variable expression in tumors and correlation with patient survival also point to its utility as a prognostic or predictive biomarker. However, possible expression in non-malignant contexts and immune evasion by tumors through ULBP1 downregulation are key considerations for therapeutic development

Other names

UL16-binding protein 1ULBP1N2DL1RAET1IN2DL-1NKG2D ligand 1ALCAN-betaretinoic acid early transcript 1INKG2DL1

Immune cell activation via NKG2D-ULBP1 binding, promoting cytotoxic killing of abnormal (tumor/infected) cells CAR-T cell-based therapies utilize NKG2D domain to target ULBP1-expressing tumor cells Monoclonal antibodies inhibiting ULBP1 to modulate immunity