RNF40 (Ring Finger Protein 40) is an E3 ubiquitin ligase that plays a critical role in histone H2B monoubiquitination at lysine 120 (H2Bub1), which is essential for gene regulation and chromatin remodeling. This protein is involved in various biological processes, including DNA damage repair, apoptosis, and cancer development. Recent studies have highlighted its dual roles in cancer progression. For example, in triple-negative breast cancer (TNBC), RNF40 supports cancer stem cell properties and glycolytic programs, promoting tumor aggressiveness. Additionally, RNF40 regulates lipid metabolism by targeting LIMA1 for proteasome-mediated degradation, thereby influencing cellular sensitivity to lipid synthesis inhibitors. These findings underscore RNF40's multifaceted roles in epigenetic regulation and cancer biology, making it a potential therapeutic target.
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