Even though, sparse studies have shown alteration of the levels of some Ubls in liver fibrosis, namely ATG12 related to autophagy [40], Fat10 and UFM1 [41], and ISG15 specifically in hepatitis C [42], in this Review, we will specially focus on the relevance of NEDD8 and SUMO proteins in liver fibrosis, whose therapeutic role has been addressed in liver fibrosis. The gene discussed is ISG15; the disease is Hepatic fibrosis.