In addition to the UPS system, the ISGylation of activated proteins [20] was also enhanced, as suggested by the upregulation of the ISG15 ubiquitin-like modifier (ISG15) in keratinized OSCC (Supplementary Table 6), and, as indicated by its differentiation, ISG15 was overexpressed in keratinized WD OSCC compared to MD/PD/WD-metastatic OSCC. This evidence concerns the gene ISG15 and Wilson disease.