Interferon-stimulated gene 15 (ISG15), a type I IFN-dependent transcript, is a member of the ISG protein family that encodes a ubiquitin-like protein.[34,35] ISG15 has complex biological links, on the one hand, to the covalent intracellular modification of target proteins (ISGylation, a process similar to ubiquitinylation) and, on the other hand, plays a role as an extracellular signaling molecule/cytokine.[36] ISG15 is thought to play a critical role in innate immune responses, the progression of immune diseases, and anti-tumor reactions.[37]. This evidence concerns the gene ISG15 and immune system disorder.