TRIM47, a member of the tripartite motif-containing protein family, functions as an E3 ubiquitin ligase. It is involved in multiple biological processes and signaling pathways, such as the NF-κB, MAPK, and ubiquitin-proteasome systems, which are crucial for inflammation, cell death, and cancer progression [1-10]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions.

In LPS-induced acute lung injury, TRIM47-deficient mice showed resistance to the injury and death, as TRIM47 aggravates the injury via promoting K63-linked ubiquitination of TRAF2, which activates NF-κB and MAPK signaling pathways to trigger an inflammatory response in endothelial cells [1]. In hepatocellular carcinoma, knockdown of TRIM47 in vitro induced ferroptosis, mainly through the CDO1-mediated regulation of GSH synthesis [2]. In gastric cancer, knockdown of TRIM47 inhibited cell proliferation, migration, and invasion, while overexpression promoted these behaviors, and it was found that TRIM47 promotes K48-linked ubiquitination and degradation of CYLD, thereby activating the NF-κB pathway [3].

In conclusion, TRIM47 plays diverse and significant roles in various biological processes and diseases. Studies using KO or knockdown models have revealed its roles in inflammation-related diseases like acute lung injury and asthma, as well as in multiple cancers. These models have provided crucial insights into how TRIM47 functions through different signaling pathways, offering potential therapeutic targets for these diseases.