ZC3H18 (zinc finger CCCH-type containing 18) is a multifunctional nuclear RNA-binding protein that plays critical roles in RNA metabolism, transcriptional regulation, and DNA repair. The protein functions as a component of nuclear RNA surveillance complexes, where it binds to cap-binding complex (CBC)-bound transcripts and associates with the nuclear exosome targeting (NEXT) complex to influence RNA fate decisions between production and degradation pathways 1. ZC3H18 serves as a transcriptional activator, specifically binding to the BRCA1 promoter at an E2F site to facilitate E2F4 recruitment and promote BRCA1 transcription, thereby supporting homologous recombination DNA repair 2. The protein undergoes histidine methylation by CARNMT1 on its C3H zinc finger domain 3. In cancer contexts, ZC3H18 exhibits oncogenic properties through multiple mechanisms: it participates in a transcriptional network with STAT3, MYC, and viral EBNA1 to regulate survival and proliferation in EBV-positive lymphomas while enhancing NF-κB signaling 4; recurrent truncating mutations in ZC3H18 stabilize endogenous retroviral RNA, contributing to oncogenesis 5; and it collaborates with HNRNPU to regulate SOX9 transcription in liver cancer stem cells 6. ZC3H18 overexpression correlates with poor prognosis in esophageal cancer, where it promotes tumor cell proliferation and invasion 7.