DDX17 is a multifunctional DEAD-box RNA helicase with both catalytic and scaffolding roles across diverse cellular processes. As an ATP-dependent helicase, DDX17 unwinds RNA and modulates RNA structures to regulate alternative splicing of AC-rich exons, including CD44 transcripts, and influences splicing of steroid hormone signaling mediators 123. DDX17 binds pri-microRNAs via specific consensus sequences and is required for processing subsets of microRNAs including miR-21 and miR-125b1 45. Beyond RNA processing, DDX17 functions as a context-dependent transcriptional coactivator or corepressor, synergizing with TP53 for MDM2 activation and cooperating with CTNNB1 to activate MYC and other oncogenic targets 67. DDX17 also mediates estrogen and testosterone signaling pathways through both helicase-dependent splicing and helicase-independent transcriptional mechanisms 83. In immunity, DDX17 restricts bunyavirus infection in an interferon-independent manner while promoting antiviral mRNA degradation 9. Clinically, DDX17 dysregulation associates with multiple disease states: overexpression promotes hepatocellular carcinoma metastasis via PXN-AS1 splicing and CXCL8 transactivation 1011, while de novo variants cause neurodevelopmental disorders with intellectual disability and motor delay 12. DDX17 downregulation occurs in heart failure but protects cardiac function through BCL6-DRP1-mediated mitochondrial homeostasis 13, and functions as an HBV restriction factor 14. These multifaceted roles underscore DDX17 as a critical regulator of gene expression with significant therapeutic potential.