DDX55 (DEAD-box helicase 55) is a nucleoplasmic RNA helicase with dual roles in ribosomal biogenesis and cellular homeostasis. Primary function: DDX55 catalyzes ATP-dependent RNA remodeling, with its C-terminal region conferring specificity for double-stranded RNA substrates 1. It is recruited to domain IV of the 28S rRNA and is essential for maturation of large ribosomal subunit precursor rRNAs 1. Mechanistically, DDX55 also regulates alternative polyadenylation (APA) of mRNA 3'UTRs, particularly at polyadenylation sites containing RNA secondary structures 2. Beyond ribosomal functions, DDX55 maintains naïve T cell homeostasis by suppressing activation-promoting transposable elements through direct binding to the MYC transcription factor, preventing TE-derived R loops and genomic instability 3. In hepatocellular carcinoma, DDX55 is significantly upregulated and promotes progression by interacting with BRD4 to activate PIK3CA transcription and β-catenin signaling, while also functioning in exosome-mediated intercellular communication 4. Clinical significance: DDX55 serves as a prognostic biomarker in HCC with strong predictive value for recurrence-free and overall survival 4. Lower baseline plasma DDX55 levels predict positive response to mesenchymal stem cell therapy in severe COVID-19 5. DDX55 is incorporated into a genomic-clinicopathologic nomogram for predicting early HCC recurrence after resection 6.