Nedd8 is a ubiquitin-like protein that is conjugated to substrates through a cascade of E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Conjugation of Nedd8 to target proteins (neddylation) regulates their activity, stability, subcellular localization, or macromolecular interactions. The best-characterized substrates of neddylation are cullins, essential components of cullin-RING E3 ubiquitin-ligase complexes. Neddylation has been implicated in various cellular processes including cell cycle progression, metabolism, immunity, and tumorigenesis. (Adapted from PMID:28234446 and PMID:33025631.)