Rnf149, or ring finger protein 149, is an E3 ubiquitin ligase. It plays a crucial role in multiple biological processes by mediating ubiquitination-a process that can lead to protein degradation or altered protein function. It is involved in pathways related to inflammation, immune response, and cell proliferation. Understanding its function is important as it impacts various disease-related processes, and genetic models such as gene knockout (KO) mouse models are valuable tools for its study [1-6].

In macrophage-related processes, knockout of Rnf149 in murine models of myocardial infarction (MI) exacerbated cardiac dysfunction. It increased infiltration of pro-inflammatory monocytes/macrophages and impaired infarct healing. Rnf149 restricts inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1) in infiltrated macrophages [1]. In lipopolysaccharide/Toll-like receptor 4 (LPS/TLR4) signal transduction, Rnf149 negatively regulates the process by mediating ubiquitination-induced CD63 degradation [2]. In hepatocellular carcinoma (HCC), overexpression of Rnf149 significantly promoted cell proliferation, migration, and invasion, and it was upregulated in tumor tissues. It stimulated HCC progression via its E3 ubiquitin ligase activity and DNAJC25 was identified as its new substrate [3]. In esophageal squamous cell carcinoma (ESCC), Rnf149 was upregulated and high expression was associated with poor prognosis. It conferred cisplatin resistance by destabilizing PHLPP2 and activating the PI3K/AKT signalling pathway [4]. In acute myeloid leukaemia (AML), RNF149 accelerates AML progression, modifies the immune milieu, triggers CD8+T cell dysfunction, and influences drug resistance [5]. In antiviral immune responses, RNF149 modulates the type I IFN innate antiviral immune responses by degrading IRF3 [6].

In conclusion, Rnf149, as an E3 ubiquitin ligase, has a wide-reaching impact on various biological functions including immune response, inflammation, and cell proliferation. KO mouse models have been instrumental in revealing its role in diseases such as myocardial infarction, different types of cancers, and in immune-related processes. These findings suggest that Rnf149 could potentially be a therapeutic target for these disease conditions.