RBPJ (recombination signal binding protein for immunoglobulin kappa J region) is a central transcriptional regulator in the Notch signaling pathway that controls cell fate determination and immune responses. RBPJ functions as a transcriptional repressor in the absence of Notch signaling and as an activator when complexed with Notch intracellular domain 1. In immune cells, RBPJ regulates critical differentiation processes: it controls monocyte-to-macrophage transition in liver disease, with RBPJ deficiency promoting protective Ly6Clo monocytes and reducing inflammatory macrophages 2. RBPJ also negatively regulates FOXP3 expression in T cells, and its knockout enhances regulatory T cell differentiation and stability through DNA demethylation mechanisms 1. In cancer immunity, RBPJ promotes differentiation of intermediate exhausted T cells to terminal exhausted T cells, and targeting RBPJ enhances T cell functional reprogramming and immunotherapy efficacy 3. Beyond immune function, RBPJ maintains mitochondrial DNA integrity by regulating TFAM expression in macrophages 4 and promotes inflammatory responses in metabolic liver disease 5. These findings establish RBPJ as a key regulator of immune cell fate and function with therapeutic implications for autoimmune diseases, cancer immunotherapy, and metabolic disorders.