When ISG15 is involved in inflammation

Interferon-stimulated gene 15 (ISG15), a key ubiquitin-like modifying molecule, plays an important role in regulating inflammatory responses. This review summarizes the functions of ISG15 in different inflammatory diseases. On the one hand, ISG15 precisely regulates the activity of signaling proteins through its intracellular modification function, thereby affecting the type I interferon signaling pathway; on the other hand, free extracellular ISG15 can act as a cytokine, activating immune cells and exacerbating inflammatory responses. We further explored the specific mechanisms of ISG15 in skin inflammation, cardiovascular inflammation, neuroinflammation, and other types of inflammation and analyzed the limitations of current studies. Finally, this study highlights the potential value of targeting the ISG15 pathway as a new strategy for the treatment of inflammatory diseases.