Traf5, short for Tumor necrosis factor receptor-associated factor 5, is a crucial adaptor molecule in the tumor necrosis factor receptor-associated factor (TRAF) family. It plays important roles in various biological processes, especially in the host innate immune responses. Traf5 is involved in multiple signaling pathways, such as the NF-κB, type I IFN, and MAPK signaling pathways [2].

In different disease models, Traf5 shows diverse functions. In a Traumatic Brain Injury (TBI) mouse model, inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype, and genetic deletion of CD36, which is related to Traf5-MAPK pathway, ameliorated TBI-induced white matter injury [1]. In myocardial I/R injury mouse models, Traf5 knockout mice exhibited heavier heart damage, inflammatory response and cell death, indicating that Traf5 protects against myocardial ischemia reperfusion injury via AKT signaling [3]. In colitis mouse models, TRAF5-/-CD4+ CD45RBhigh T cells transferred to Rag2-/-mice showed more severe intestinal inflammation, and knockout of Runx1 inhibited the differentiation of TRAF5-/-CD4+ T cells into Th1 and Th17 cells, suggesting that TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 in colitis [4]. In hepatocellular carcinoma (HCC) cell lines and xenograft models, silencing of TRAF5 enhanced necroptosis in HCC by inhibiting LTBR-mediated NF-κB signaling [5].

In conclusion, Traf5 is a key molecule in immune-related signaling pathways. Gene knockout mouse models have revealed its significant roles in multiple disease conditions, including TBI-related white matter injury, myocardial I/R injury, colitis, and HCC. Understanding the function of Traf5 in these models helps to deeply understand the pathogenesis of these diseases and provides potential therapeutic targets.