IFI27, an interferon (IFN)-stimulated gene, is emerging as a crucial player in immune responses across various species, with significant implications for precision medicine. Commonly found among the most upregulated genes in infections, cancers, as well as inflammatory and autoimmune disorders, IFI27 is ready to be trialed in clinical practice for certain indications, and holds promise as an immunomodulatory target. We hypothesize that IFI27 plays a dual role, typically supporting immune defense but sometimes contributing to disease progression, which might render it a putative biomarker for diagnosis, prognosis, and treatment response. We advocate for focused research on IFI27 to unlock its potential in precision medicine and to contribute to a unifying framework of its mechanisms in the immune response. Our viewpoint is supported by numerous studies highlighting IFI27's involvement across various conditions and the possibilities for clinical application.