DDX18 is an ATP-dependent RNA helicase with dual roles in RNA metabolism and pluripotency regulation. Mechanistically, DDX18 resolves R-loops at transcribed genes and DNA lesion sites through PARP-1-mediated recruitment 1, preventing replication defects and genome instability. Loss of DDX18 causes aberrant R-loop accumulation, impaired DNA repair foci formation, and γH2AX accumulation 1. In pluripotent cells, DDX18 safeguards ribosomal DNA by antagonizing PRC2-mediated H3K27me3 deposition, maintaining active rRNA transcription and ribosomal biogenesis essential for embryonic stem cell self-renewal 2. DDX18 coordinates nucleolus phase separation through NPM1 interaction, regulating centromere clustering and perinucleolar heterochromatin formation 3. Clinically, DDX18 is upregulated in multiple cancers with distinct mechanisms: in pancreatic cancer, it promotes STAT1-mediated PD-L1 expression driving immune escape 4; in esophageal cancer, YY1-induced DDX18 activates AKT/mTOR signaling to enhance EMT and proliferation 5; in head and neck cancer, ALKBH1-mediated DDX18 upregulation promotes cell proliferation 6. Early zebrafish studies identified DDX18 mutations in acute myeloid leukemia associated with p53-dependent cell-cycle arrest 7. Rare non-coding variants affecting DDX18 polyadenylation show disease associations 8.