DDX56 is a DEAD-box RNA helicase with dual and opposing roles in viral infections and cancer. In viral pathogenesis, DDX56 functions as a proviral host factor that enhances replication of multiple RNA viruses. DDX56 interacts with influenza A virus NS1 protein to promote viral replication 1, cooperates with foot-and-mouth disease virus 3A protein to inhibit IRF3 phosphorylation and suppress type I interferon production 2, and antagonizes IFN-β production during encephalomyocarditis virus infection by blocking IRF3 nuclear translocation 3. Notably, DDX56 also demonstrates antiviral properties against alphaviruses like chikungunya virus, where it relocates to the cytoplasm and binds viral genomic RNA stem-loops to destabilize incoming viral genomes 4. As an RNA helicase, DDX56 plays context-dependent roles in intrinsic and innate immunity 5. In oncogenic contexts, DDX56 is significantly upregulated in multiple cancers. In hepatocellular carcinoma, DDX56 transcriptionally activates MIST1 through histone methylation to promote proliferation via PTEN-AKT pathway dysregulation 6. In lung adenocarcinoma, DDX56 reduces apoptosis and carboplatin sensitivity by promoting Bcl-2 transcription and activating NF-κB signaling 7. In colorectal cancer, DDX56 amplification promotes oncogenic alternative splicing and cell cycle progression by downregulating WEE1 8. High DDX56 expression correlates with poor prognosis and metastasis across multiple cancers, identifying it as a potential therapeutic target.