Neddylation is a post-translational protein modification that conjugates a 
ubiquitin-like protein NEDD8 to target proteins. Similar to ubiquitination, 
neddylation is mediated by a cascade of three NEDD8 specific enzymes, an E1 
activating enzyme, an E2 conjugating enzyme and one of the several E3 ligases. 
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, cell signaling etc. Dysregulation of 
neddylation has been linked to cancer, neurodegenerative disorders, and more 
recently, cardiac disease. Here we comprehensively overview the biochemistry, 
the proteome and the biological function of neddylation. We also summarize the 
recent progress in revealing the physiological and pathological role of 
neddylation and deneddylation in the heart.