IRF2BP2 (interferon regulatory factor 2 binding protein 2) functions as a transcriptional corepressor that plays critical roles in immune regulation and cellular homeostasis. The protein acts as an IRF2-dependent transcriptional repressor and represses NFAT1-dependent transactivation of NFAT-responsive promoters 1. IRF2BP2 regulates inflammatory responses by repressing IL1β/TNFα signaling via NFκB, and its perturbation results in acute inflammatory states 2. The protein also functions in metabolic sensing, where L-malate disrupts BiP-IRF2BP2 interaction in a pH-dependent manner, protecting IRF2BP2 from degradation and modulating inflammatory responses in macrophages 3. In cancer contexts, IRF2BP2 exhibits complex roles - it acts as a tumor suppressor in acute myeloid leukemia where its loss leads to cell death through unleashed inflammation 2, but can also promote neuroblastoma proliferation through super-enhancer regulation and ALK pathway activation 4. Clinically, IRF2BP2 deficiency causes common variable immunodeficiency characterized by impaired B-cell maturation, reduced memory B cells, poor immunoglobulin production, and inflammatory complications including gastrointestinal disorders 5. The protein's dysfunction is also implicated in Richter syndrome transformation from chr1 lymphocytic leukemia 6.