Silencing Ubc9, the only known E2-conjugating enzyme in SUMOylation, alleviates hepatic stellate cell activation, while silencing RNF4, an E3 ubiquitin ligase family member, facilitates the TGF-β/Smad pathway and causes liver fibrosis by enhancing SUMOylated PML accumulation (Dai et al., 2020; Li et al., 2024a). The gene discussed is TGFB1; the disease is Hepatic fibrosis.