DDX51 is an ATP-binding RNA helicase primarily involved in 60S ribosomal subunit biogenesis [UniProt]. Beyond its canonical role, DDX51 has emerged as a multifunctional protein with significant disease relevance. In cancer biology, DDX51 promotes proliferation across multiple malignancies. In non-small cell lung cancer, DDX51 knockdown reduces cell proliferation and induces S-phase arrest through dysregulation of multiple signaling pathways, with in vivo tumor suppression demonstrated in animal models 1. Similarly, in esophageal squamous cell carcinoma, DDX51 knockdown inhibits cell proliferation, promotes apoptosis, and reduces migration/invasion by inactivating the PI3K/AKT pathway; genetic evidence from rescue experiments confirms AKT as a critical effector 2. DDX51 mutations are significantly recurrent in malignant pleural mesothelioma, identified alongside alterations in RNA helicase signaling pathways 3. Beyond cancer, DDX51 was identified as a host factor critical for SARS-CoV-2 replication in genome-wide CRISPR screens, suggesting roles in viral-host interactions 4. In acute lymphoblastic leukemia, DDX51 methylation status differentiated B-cell and T-cell subtypes, indicating epigenetic dysregulation in leukemogenesis 5. These findings collectively suggest DDX51 represents a promising therapeutic target across multiple cancer types and potentially in viral diseases.