NFE2L2 and CUL3 mutations have been identified in HNSCC at a frequency of 6% and 4%, respectively, with mutations in NFE2L2 mapping onto regions encoding the Neh2 domain of NRF2 and mutations in CUL3 occurring in regions encoding amino acids 33–66 in the CR1 domain. Here, NFE2L2 is linked to head and neck squamous cell carcinoma.