ISG15 and cancer: Through covalent ISGylation, ISG15 regulates oncogenic pathways, such as kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and mitogen‐activated protein kinases (MAPK) pathways, by affecting the stability and/or function of the substrate proteins.[22] Additionally, extracellular free ISG15 can function as an immunomodulatory cytokine, regulating immune cell function against cancer.[22] However, little is known about the role of intracellular unconjugated free ISG15.