RNF111 is an E3 ubiquitin ligase that functions as a critical regulator of TGF-β/BMP signaling and DNA repair pathways. As an SUMO-targeted ubiquitin ligase, RNF111 binds polysumoylated chains through SUMO interaction motifs and mediates K63-linked ubiquitination of sumoylated substrates 1. In the BMP pathway, RNF111 enhances SMAD2/SMAD3 transcriptional activity by promoting proteasomal degradation of SMAD inhibitors, particularly SMAD7, and also couples SMAD effector activation with their degradation 23. In nucleotide excision repair, RNF111 promotes UV-lesion repair by catalyzing K63-linked ubiquitylation of SUMOylated XPC, facilitating its release from damaged DNA and enabling recruitment of NER endonucleases 4. RNF111 is predominantly expressed in oocytes and is essential for female fertility; deleterious variants cause premature ovarian insufficiency through dysregulation of BMP signaling in developing ovaries, accounting for 0.78% of POI cases 5. During embryonic development, RNF111 is required for epiboly progression and mesoderm patterning 6. Additionally, RNF111 participates in regulating selective estrogen receptor degradation and immune cell metabolism through the RNF111/OGT pathway 78. These diverse functions establish RNF111 as a multifunctional ubiquitin ligase critical for developmental, reproductive, DNA repair, and immune processes.