DDX49 is an ATP-dependent RNA helicase with multifaceted roles in RNA metabolism and cellular homeostasis. Structurally, DDX49 possesses conserved helicase activity and a novel nuclease activity dependent on active site aspartate residues 1, required to maintain 5.8S rRNA levels and support cell proliferation through pre-ribosomal RNA regulation 21. Beyond canonical RNA processing, DDX49 exhibits antiviral activity by recognizing gammaherpesvirus transcripts during lytic reactivation, particularly KSHV immediate-early and early mRNAs, thereby suppressing viral replication and stimulating interferon responses 3. Recently, DDX49 was identified as a component of lipid-induced granules in hepatocytes, where it undergoes liquid-liquid phase separation triggered by arachidonic acid metabolites to restrain metabolic dysfunction-associated steatotic liver disease-related fibrosis through selective mRNA sequestration 4. Clinically, DDX49 overexpression correlates with poor prognosis across multiple malignancies including lung, breast, prostate, and hepatocellular carcinoma, where it promotes proliferation, migration, and metastasis via Akt/β-catenin and JAK-STAT signaling pathways 56789. These findings establish DDX49 as both a potential biomarker for lymph node metastasis and a therapeutic target in cancer treatment.