TGF-β activated kinase-1 binding protein-1 (TAB1) binds and induces autophosphorylation of TGF-beta activating kinase (TAK1). TAB1 is an upstream adaptor for the activation of the kinase TAK1, which in turn couples to the NF-kappaB pathway. TAB1 forms the protein complex with TAK1 and enhances its kinase activity in the human and mammals. TAK1, a mitogen-activated kinase kinase kinase, is involved in several distinct signaling pathways including non-Smad pathways for TGF-beta superfamily members and inflammatory responses caused by cytokines. Conventional disruption of the murine Tab1 gene results in late gestational lethality showing intraventricular septum defects and underdeveloped lung alveoli. A single O-GlcNAc site has been identified on human TAB1 that modulates TAK1-mediated cytokine release in cells.