TAB1 is a key adapter protein that activates the MAPKKK family member TAK1 (MAP3K7), enabling inflammatory signal transduction in response to toll-like receptor and cytokine stimulation. Mechanistically, TAB1 associates with TAK1's catalytic domain to trigger its autophosphorylation and full activation, and similarly facilitates MAPK14 autophosphorylation and activation. TAB1 also recruits MAPK14 to phosphorylate regulatory TAB2 and TAB3 subunits, with MAPK14 subsequently phosphorylating TAB1 itself to provide feedback inhibition of TAK1. This TAB1-TAK1 axis drives downstream NF-κB and JNK signaling to promote proinflammatory cytokine production. TAB1 dysfunction has been associated with congenital heart defects and coronary artery disease. Notably, TAB1 homozygous knockout is embryonic lethal in mice, with mutant embryos showing severe cardiovascular and lung dysmorphogenesis, indicating critical developmental roles. In clinical contexts, TAB1 modulation shows therapeutic potential: in glioblastoma, suppressing the TAB1-TAK1-NF-κB-EMP1 pathway reduces invasion 1, and tofacitinib can therapeutically activate this suppression. In sepsis, platelet NLRP6-mediated TAB1 degradation protects against microvascular thrombosis and improves survival 2. Additionally, TAB1 knockdown via ginger-derived exosomal miRNAs alleviates colitis by downregulating NF-κB-mediated inflammation 3. Recent Mendelian randomization analysis identified brain TAB1 as a candidate druggable target for cognitive performance 4.