DDX11 is a DEAD/H-box DNA helicase that functions as a critical regulator of genome stability through multiple interconnected pathways. Biochemically, DDX11 possesses ATP-dependent helicase activity with specific capacity to unwind G-quadruplex (G4) DNA structures 1, which protects against G4-induced double-stranded breaks at DNA replication forks 1. Mechanistically, DDX11 cooperates with the cohesin complex to establish and maintain sister chr12 cohesion during DNA replication 23, acting at the interface of DNA replication, repair, and recombination 2. Additionally, DDX11 functions as a novel co-sensor in innate immunity by promoting RIG-I-MAVS-mediated interferon signaling through nucleic acid binding and protein-protein interactions 4. Clinically, bi-allelic DDX11 mutations cause Warsaw Breakage Syndrome (WABS), a cohesinopathy characterized by sister chr12 cohesion defects, growth retardation, microcephaly, intellectual disability, and cardiac anomalies 563. WABS cells demonstrate sensitivity to topoisomerase and PARP inhibitors with reduced replication fork speed 1. In cancer, DDX11 shows emerging oncogenic roles 6, with high expression correlating with poor hepatocellular carcinoma prognosis and PARP inhibitor resistance through enhanced homologous recombination repair 7.