NAE (NEDD8-activating enzyme) is a key enzyme initiating NEDDylation, a protein modification process similar to ubiquitination, responsible for activating NEDD8, a small regulatory protein, thereby regulating the functions of specific substrate proteins through covalent attachment. NAE is primarily composed of the NAE1 subunit and the UBA3 subunit, forming an active complex. This process is crucial for cell cycle progression, signal transduction, and protein degradation. The activity and expression of NAE are specific to different cell types and tissues, with abnormal expression or mutations associated with cancer development and dysregulated cell proliferation.