NFE2L2 and goiter: However, regardless of any broader relevance for the pathogenesis of goiter, these cases are important because they suggest that there may be some particularities regarding Keap1/Nrf2 signaling in the thyroid as compared to other tissues: It can be reasonably assumed that in the patients harboring germline KEAP1 loss-of-function mutations, Nrf2 was activated in all tissues.