By utilizing AKR1B10 as a biomarker for NRF2 activation, we found only 11 samples with NRF2 activation and a candidate mutation in UBE2M, NAE1, NEDD8, or the NEDD8-binding domain of CUL3. This suggests that defective neddylation is not a common mechanism driving NRF2 activation in cancers. Here, CUL3 is linked to cancer.