DDX39A (DExD-box helicase 39A) is an RNA helicase that plays essential roles in RNA metabolism, particularly in mRNA export and splicing regulation 1. The protein functions as an ATP-dependent helicase that facilitates nuclear mRNA export to the cytoplasm and regulates alternative splicing patterns 1. DDX39A demonstrates functional redundancy with its paralog DDX39B but also exhibits substrate specificity, with certain pre-mRNAs requiring one paralog over the other based on their polypyrimidine tract characteristics 1. In genome stability maintenance, DDX39A resolves RNA-DNA hybrids at replication forks, balancing fork protection and processing by facilitating controlled DNA2-mediated resection and fork restart 23. The protein plays a complex role in innate immunity by negatively regulating type I interferon production through nuclear retention of antiviral transcripts, with this function modulated by SUMOylation 4. However, DDX39A also facilitates antitumor immunity by actively exporting nuclear retroelement transcripts that form cytosolic dsRNA to trigger viral mimicry responses 5. In cancer contexts, DDX39A expression is dysregulated and contributes to oncogenic programs, with splicing variants promoting tumor progression through pathways involving MYC signaling and integrin regulation 67.