NFE2L2 and neoplasm: The KEAP1-NRF2 signaling can be activated by 1) KEAP1 disassociation from NRF2; 2) NRF2 phosphorylation regulation [27]; 3) KEAP1 degradation [23, 24], etc. Recent studies have revealed that TRIM25 as a RING-type E3 ubiquitin ligase facilitates tumor cell survival by activating NRF2 signaling through ubiquitination and degradation of KEAP1 during ER stress, providing a promising therapeutic approach targeting TRIM25 concurrently with NRF2 inhibition [53].