One of the important events is type I IFN production and the subsequent upregulation of ISG15 and its related enzymes during cancer development, supporting our findings of elevated ISG15 expression and ISGylation in lung cancer tissues2 and suggesting that the upregulation of ISG15 expression and ISGylation is directly or indirectly linked to the pathogenesis of cancer. The gene discussed is ISG15; the disease is cancer.