RNF113A is an X-linked E3 ubiquitin ligase that serves dual critical functions in pre-mRNA splicing and DNA damage response. As a spliceosome component, RNF113A associates with U2, U4, and U6 snRNAs and interacts with PRP19 and BRR2 proteins, where it is essential for splicing efficiency 1. The protein catalyzes K63-linked polyubiquitination of targets including SNRNP200/BRR2 2. In DNA repair, RNF113A functions as a damage sensor that specifically responds to RNA alkylation rather than DNA alkylation 3. Upon alkylation damage, RNF113A synthesizes K63-linked polyubiquitin chains that recruit the ASCC-ALKBH3 repair complex to damaged sites, suppressing transcription and R-loop formation 23. Loss-of-function mutations in RNF113A cause X-linked trichothiodystrophy, characterized by CNS abnormalities and mental retardation 2. RNF113A deficiency impairs neural stem cell survival and differentiation by affecting p53, Nupr1, and Rad51 pathways 4. The protein also regulates CXCR4 degradation, influencing chemokine signaling 5. RNF113A shows oncogenic properties in esophageal squamous cell carcinoma and cervical cancer, promoting proliferation and invasion 65. Additionally, RNF113A has been associated with autism spectrum disorders 7.