Traf5, short for Tumor Necrosis Factor Receptor-associated Factor 5, is a crucial adaptor molecule in the immune system, participating in various TNF receptor signaling pathways [2,3]. It is involved in multiple biological processes such as inflammation, apoptosis, and cell development, and is associated with pathways like MAPK, NF-κB, and type I IFN signaling [1,3]. Genetic models, like KO mouse models, are valuable tools to study its functions.

In a study on white matter injury (WMI) after Traumatic Brain Injury (TBI), CD36 deletion was found to prevent WMI by modulating microglia polarization through the Traf5-MAPK signal pathway. Inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype [1].

In plasmacytoid dendritic cell (pDC) development, Traf5 was shown to support pDC generation in the bone marrow and contribute to pDC subset homeostasis in the periphery in a cell-intrinsic manner [2].

In myocardial ischemia reperfusion (I/R) injury, Traf5 knockout mice exhibited heavier heart damage, inflammatory response, and cell death, indicating that Traf5 protects against myocardial I/R injury via AKT signaling [4].

In colitis mice, TRAF5-/-CD4 + CD45RBhigh T cells led to more severe intestinal inflammation, and TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis [5].

In hepatocellular carcinoma (HCC), Traf5 knockdown inhibited HCC cell viability, proliferation, migration, invasion, and survival but enhanced necroptosis by suppressing LTBR-mediated NF-κB signaling [6].

In conclusion, Traf5 is essential in regulating inflammation, cell development, and apoptosis. Gene knockout mouse models have revealed its significance in diseases such as WMI after TBI, myocardial I/R injury, colitis, and HCC, providing insights into potential therapeutic strategies for these conditions.