NFE2L2 and Hyperkeratosis: Keap1–/– mice are rescued from juvenile lethality, and hyperkeratosis is largely avoided in Nrf2 heterozygous compound mutant mice (Keap1–/–::Nrf2+/–) [89], indicating that massive Nrf2 expression is required to provoke severe hyperkeratosis of the esophagus (Table 2).