DDX60L (DExD/H-box 60 like) is an interferon-stimulated gene encoding a cytoplasmic RNA helicase that functions as a direct antiviral effector in innate immunity. As a DExD/H-box helicase, DDX60L recognizes double-stranded and single-stranded RNA 1, playing roles in both viral sensing and viral restriction. DDX60L is upregulated upon viral infection and interferon treatment 2, and its knockdown increases hepatitis C virus replication while rescue experiments demonstrate it functions as an important effector of type I, II, and III interferon responses 2. DDX60L likely inhibits viral RNA replication directly rather than affecting translation or viral assembly 2. Beyond hepatitis C, DDX60L contributes to intrinsic antiviral immunity as part of a multilayered helicase network 1. Clinically, DDX60L dysregulation associates with multiple disease conditions. Polymorphisms in DDX60L correlate with nervous system involvement in Behçet's syndrome 3, and elevated DDX60L expression appears in systemic lupus erythematosus and related autoimmune conditions 4. DDX60L is also significantly upregulated in Sjögren's disease patients and correlates with specific clinical manifestations including hyperglobulinemia 5. Additionally, DDX60L functions as a novel oncogene in pancreatic ductal adenocarcinoma, with DDX60L knockdown inhibiting metastasis and inducing apoptosis through TNF and NF-κB pathway modulation 6. Genetic variants in DDX60L show nominal association with posttraumatic stress disorder risk 7.