Neddylation is a post-translational protein modification that conjugates the ubiquitin-like protein NEDD8 to target proteins. Neddylation is countered by the action of deneddylases via a process termed deneddylation. By altering the substrate's conformation, stability, subcellular localization or binding affinity to DNA or proteins, neddylation regulates diverse cellular processes including the ubiquitin-proteasome system-mediated protein degradation, protein transcription and cell signaling. Only a minority of deneddylases, including the COP9 signalosome (CSN) and NEDP1 (aka DEN1/SENP8), are NEDD8-specific, whereas the majority are also known to regulate deubiquitination. Deneddylases may be metallopeptidases (e.g. CSN) or cysteine-type peptidases (e.g. NEDP1). (Adapted from PMID:25628956.)