TAB2 is an adapter protein that functions as a central scaffold in inflammatory signaling pathways 1. It recognizes Lys-63-linked polyubiquitin chains through its RanBP2-type zinc finger domain and links MAP3K7/TAK1 and TRAF6 to organize signaling complexes that promote activation of NF-κB and MAPK pathways in response to TNFα, IL-1β, and toll-like receptor ligands 1. TAB2 plays critical roles in heart development, as evidenced by its involvement in congenital heart defects 2. Pathogenic TAB2 variants cause a syndromic presentation featuring distinctive facial features, growth abnormalities, developmental delay, and cardiac disease 2. TAB2 genetic variants are associated with dilated cardiomyopathy susceptibility and prognosis in human populations 34. Beyond cardiac disease, TAB2 polymorphisms influence epithelial ovarian cancer susceptibility 5. TAB2 activity is regulated post-translationally: USP25 deubiquitinates TAB2 to suppress neuroinflammation after ischemic stroke 6, while RNF99 ubiquitinates TAB2 to dampen excessive TLR-mediated inflammatory responses 7. These regulatory mechanisms highlight TAB2's importance in balancing inflammatory signaling across physiological and pathological contexts.