The unique allosteric binding mode of capsaicin to KEAP1 presents an exciting opportunity for the development of more potent and selective NRF2 activators. By targeting specific allosteric sites on KEAP1, researchers can design molecules that interact with KEAP1 in a non-covalent manner, avoiding the potential off-target effects associated with covalent modifications. This approach allows for the creation of compounds that can modulate the KEAP1-NRF2 interaction with high specificity, enhancing the therapeutic efficacy of NRF2 activation. Leveraging the allosteric binding mode of capsaicin can lead to the development of novel lead compounds with improved pharmacokinetic properties and reduced side effects, paving the way for the discovery of more effective NRF2 agonists.