Neural Precursor Cell Expressed Developmentally Downregulated Gene 8 (NEDD8), also known as Related to Ubiquitin 1 (Rub1), is a 6-8 kDa member of the Ubiquitin family of proteins. Human NEDD8 is activated by a distinct NEDD8-activating (E1) enzyme, a heterodimeric complex composed of APPBP1 and UBA3 subunits . Activated NEDD8 is subsequently transferred to the UBE2M/Ubc12 or UBE2F NEDD8-conjugating (E2) enzymes . Through a process termed neddylation, the ROC1/Rbx1 RING Finger E3 ligase transfers NEDD8 to specific substrates. NEDD8 plays a critical regulatory role in cell proliferation and dysregulation of the NEDD8 pathway has been associated with several cancer pathologies .