SERTAD3 (SERTA domain containing 3) is an interferon-stimulated antiviral protein and transcriptional coactivator with dual roles in innate immunity and cell growth regulation. As an antiviral factor, SERTAD3 inhibits multiple viruses through distinct mechanisms: it disrupts influenza A virus RNA-dependent RNA polymerase (RdRp) complex formation by interacting with PB2, PB1, and PA proteins 1, promotes proteasomal degradation of Zika virus capsid protein via nucleolar interaction 2, and inhibits porcine reproductive and respiratory syndrome virus by targeting the Nsp9 RdRp domain 3. A conserved eight-amino-acid motif mediates these antiviral functions and has therapeutic potential 12. Clinically, SERTAD3 represents a cancer-relevant gene with oncogenic potential. Located within the amplified 19q13 chr19 region, SERTAD3 overexpression induces E2F transcriptional activity and promotes tumor growth in cell and mouse models 4. Its upregulation in tamoxifen-resistant breast cancer occurs through the HNF1A-AS1/miR-363 axis, contributing to drug resistance 5. SERTAD3 overexpression correlates with aggressive retinoblastoma phenotypes 6. Additionally, chromosome 19 variants harboring SERTAD3 associate with childhood otitis media susceptibility 7. SERTAD3 transcriptional activity is negatively regulated by I-mfa domain proteins 8, providing a potential regulatory checkpoint.