Rnf149, or ring finger protein 149, is an E3 ubiquitin ligase. E3 ubiquitin ligases play a crucial role in the ubiquitination process, which tags proteins for degradation or modulates their functions, thus participating in various cellular pathways and biological processes [1,2,3,4,5,6].

In myocardial infarction (MI), Rnf149 is highly expressed in murine and human cardiac macrophages at the early phase. Knockout of Rnf149, transplantation of Rnf149 -/- bone marrow, and bone marrow macrophage-specific Rnf149-knockdown exacerbated cardiac dysfunction in murine MI models. It was found that Rnf149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1, and loss of IFNGR1 rescued the deleterious effects of Rnf149 deficiency on MI. Also, STAT1 activation induced Rnf149 transcription, creating a feedback control mechanism to fine-tune macrophage-driven inflammation [1].

In lipopolysaccharide/Toll-like receptor 4 (LPS/TLR4) signal transduction, Rnf149 negatively regulates by mediating ubiquitination-induced CD63 degradation, as it can directly interact with CD63 and degrade it through covalent modification [2].

In hepatocellular carcinoma (HCC), Rnf149 is strikingly upregulated in tumor tissues, and overexpression promotes cell proliferation, migration, and invasion via its E3 ubiquitin ligase activity, with DNAJC25 identified as its new substrate [3].

In esophageal squamous cell carcinoma (ESCC), Rnf149 is upregulated and confers cisplatin resistance by interacting with PHLPP2 and inducing its E3 ligase-dependent protein degradation, activating the PI3K/AKT signalling pathway [4].

In conclusion, Rnf149, as an E3 ubiquitin ligase, plays important roles in multiple biological processes and disease conditions. Gene knockout or knockdown studies in mouse models have revealed its functions in cardiac repair post-infarction, immune signal transduction, and cancer progression. These findings highlight the significance of Rnf149 as a potential therapeutic target in relevant diseases such as MI, HCC, and ESCC.