DDX23 (DEAD-box helicase 23) is a multifunctional RNA helicase with primary roles in pre-mRNA splicing and innate antiviral immunity. In splicing, DDX23 functions as a spliceosomal component whose phosphorylation by SRPK2 is required for B complex formation 1. DDX23 interacts directly with SR protein SRSF1, with its N-terminal RS-like domain mediating spliceosome incorporation and the transition from pre-B to B spliceosome complexes 2. Beyond splicing, DDX23 suppresses incorrect R-loops formed during transcription 3. DDX23 functions as an evolutionarily conserved dsRNA sensor that translocates from nucleus to cytoplasm upon viral detection, forming complexes with TRIF or MAVS to activate NF-ΞΊB and IRF3 signaling during innate immune responses 4. In viral infections, DDX23 negatively regulates FMDV IRES-dependent translation and replication, though the virus degrades DDX23 via 3C proteinase 5. Clinically, elevated DDX23 m6A methylation promotes pancreatic ductal adenocarcinoma progression and gemcitabine resistance through PI3K/Akt signaling activation 6. Additionally, pharmacological promotion of SDC4/DDX23 complex formation induces hepatocellular carcinoma genomic instability 7. These findings establish DDX23 as a multivalent regulator of RNA metabolism and immunity with therapeutic relevance in cancer and viral diseases.