DDX42 is an ATP-dependent RNA helicase that catalyzes bidirectional RNA duplex dynamics 1. ATP binding and hydrolysis trigger RNA strand separation, while the ADP-bound form promotes complementary strand annealing 1. DDX42 is essential for spliceosome assembly, transiently associating with the SF3B subcomplex during 17S U2 SnRNP complex formation before being released post-assembly 2. Additionally, DDX42 functions as an intrinsic antiviral factor restricting positive-strand RNA viruses including HIV-1, CHIKV, and SARS-CoV-2, likely through direct interaction with viral ribonucleoprotein complexes 3. It also inhibits LINE-1 retrotransposition 3. DDX42 regulates cell survival by interacting with TP53BP2 to counteract apoptosis and relocalizing TP53BP2 to the cytoplasm 4. Clinically, DDX42 overexpression is associated with hepatocellular carcinoma progression and treatment resistance, promoting cell proliferation and reducing sensitivity to radiotherapy and sorafenib through GRB2 mRNA maturation and PI3K/AKT pathway activation 5. Elevated DDX42 expression in carotid atherosclerotic plaques correlates with increased malignancy-related pathway activation 6. DDX42 has been identified as a G4-binding protein involved in G-quadruplex biology 7. Finally, DDX42 fusion partners with ZNF384 have been implicated in acute lymphoblastic leukemia 8. Post-translational modification and protein-protein interactions regulate DDX42 activity in various cellular contexts 9.