DDX60 is a DExD/H-box RNA helicase that serves as a positive regulator of antiviral interferon responses. Primary Function: DDX60 binds single-stranded RNA, double-stranded RNA, and DNA, promoting RIG-I and MDA5-dependent type I interferon signaling upon viral detection 1. It protects dsRNA from RISC-mediated degradation, maintaining dsRNA accumulation necessary for innate immune activation 2. Mechanism: DDX60 exhibits antiviral activity against hepatitis C virus and vesicular stomatitis virus 3, with targeted specificity compared to broadly acting interferon-stimulated genes. Transcription is regulated via the STAT3-driven axis downstream of AKT-GSK3β signaling 2. Disease Relevance: KRAS-mutant colorectal cancers suppress DDX60 expression, impairing interferon responses and immune checkpoint inhibitor efficacy 2. Conversely, DDX60 is upregulated in pancreatic and head-and-neck cancers, promoting proliferation and invasion through NF-κB/IFI27 signaling 45. DDX60 also protects against ischemic cardiac injury by enhancing Arl2 translation and mitochondrial function 6. Clinical Significance: Beyond antiviral immunity, DDX60 represents a therapeutic target in multiple malignancies and ischemic heart disease, though viruses like CCHFV can hijack DDX60 for replication 7.