DDX5 (DEAD-box helicase 5) is a multifunctional RNA helicase that plays critical roles in both RNA processing and transcriptional regulation. The protein functions as a master regulator of alternative splicing, particularly in disease-relevant contexts such as cardiac function, where DDX5 regulates CaMKIIδ splicing to maintain calcium homeostasis 1. In osteoarthritis, DDX5 prevents cartilage fibrosis by controlling alternative splicing of fibrosis-related transcripts and unwinding G-quadruplex structures in the COL2 promoter 2. The helicase also contributes to genome stability by resolving R-loops through interaction with MCM8, preventing DNA damage accumulation 3. DDX5 serves as a transcriptional coactivator in various contexts, including recruitment by SMARCA5 to activate AKR1B1 transcription in leukemia 4 and interaction with β-arrestin2 to restrict NF-κB signaling in breast cancer 5. Additionally, DDX5 acts as a host restriction factor for HBV replication by promoting transcriptional readthrough and RNA destabilization 6. The protein's expression is regulated by factors such as PRP19, which promotes DDX5 ubiquitination and degradation, affecting immune cell recruitment in hepatocellular carcinoma 7. Overall, DDX5 functions as both a tumor suppressor and oncogene depending on cellular context, making it an important therapeutic target 8.