TAB3, short for TGF-β-activated kinase 1 (MAP3K7) binding protein 3, is a crucial protein in biological systems. It is an essential binding partner of TAK1, a member of the MAPK kinase kinase (MAPKKK) family. Together, they play vital roles in activating the NF-κB and MAPKs pathways, which are involved in a wide range of physiological and pathological processes, such as inflammatory responses, cell apoptosis, and proliferation [4].

In acute kidney injury (AKI), METTL3 promotes m6A modifications of TAB3 and enhances its stability via IGF2BP2-dependent mechanisms. Conditional knockout of METTL3 from mouse kidneys attenuated cisplatin-and ischemic/reperfusion-induced renal dysfunction, injury, and inflammation, suggesting that TAB3 might be involved in the renal injury and inflammation process in AKI [1].

In acute pancreatitis (AP), the expression of TAB3 was significantly increased in a caerulein-induced AP rat and cell model, and knockdown of TAB3 in AP AR42J cells reduced pro-inflammatory cytokines and inhibited p-P65 production, indicating that TAB3 may accelerate the inflammatory responses of AP through NF-κB activation [2].

In wear particle-induced osteolysis, miR-3470b in macrophage-derived exosomes targets TAB3/NF-κB signaling, and engineered exosomes enriching miR-3470b can suppress osteolysis, suggesting TAB3's role in this osteolysis process [3].

In colorectal cancer, knockdown of TAB3 significantly decreased PIM1 expression and inhibited CRC proliferation in vitro and in vivo, and TAB3 regulates PIM1 expression by promoting STAT3 phosphorylation and activation through the formation of the TAB3-TAK1-STAT3 complex [5].

In summary, TAB3 is a key player in multiple biological processes and diseases. Through gene knockout and conditional knockout mouse models, its roles in AKI, AP, osteolysis, and colorectal cancer have been revealed. These studies help to understand the biological functions of TAB3 in disease mechanisms, providing potential therapeutic targets for related diseases.