Equine Interferon-Alpha (IFN-α) is a type I interferon produced primarily by plasmacytoid dendritic cells and virus-infected epithelial and immune cells in horses (Equus caballus), where it plays a central role in early innate antiviral defense. Upon binding to the type I interferon receptor complex (IFNAR1/IFNAR2), equine IFN-α activates JAK/STAT signaling pathways, leading to induction of interferon-stimulated genes (ISGs) that inhibit viral replication, enhance antigen presentation, and promote activation of natural killer (NK) cells and adaptive immune responses. IFN-α is rapidly upregulated in response to important equine viral pathogens such as equine influenza virus, equine herpesvirus-1 and -4 (EHV-1/EHV-4), West Nile virus, and equine arteritis virus, where it contributes to viral control but may also influence inflammatory pathology if dysregulated. Modulation of type I interferon responses can affect disease severity, viral shedding, and vaccine responsiveness. In veterinary and translational research, characterization of equine IFN-α supports studies of respiratory viral pathogenesis, neuroinvasive viral disease (e.g., EHV-1 and West Nile virus), antiviral therapeutic development, and comparative type I interferon biology in large-animal systems relevant to both equine health and broader immunological research.