Abstract
Interferon-gamma (IFN-γ) is crucial for immunity against different pathogens due to its broad effects on the multiple arms of the immune system. The regulation of IFN-γ immunity is of extensive interest to research as well as practical activity for drug discovery. New evidence supports previous findings that ubiquitin-like protein ISG15 acts as an extracellular cytokine and promotes IFN-γ production, providing intriguing insights of the importance of ISG15 into the control of human mycobacterial disease.