Neddylation, a post-translational modification that adds an ubiquitin-like protein NEDD8 to substrate proteins, then affecting their stability as well as their subcellular localization, conformation, and function, has been reported to be over-activated in different human cancers, including lung cancer, intrahepatic cholangiocarcinoma, HCC, colorectal cancer, glioblastoma, nasopharyngeal carcinoma, and esophageal squamous cell carcinoma [31,42,57,58]. The gene discussed is NEDD8; the disease is hepatocellular carcinoma.