 Oxidative stress and lipid peroxidation, LPO, have been linked to various physiological and pathological processes. One of the main products of LPO is 4-hydroxanoneenol, for HNE, which has been shown to be an important mediator of cellular signaling and a secondary messenger of reactive oxygen species. For HNE can form a ducts with proteins, which are preferentially adducted with cysteine, histidine, and lysine residues. These adducts can then alter the function of target proteins, leading to changes in cellular responses such as the activation of the NRF2 slash KEEP1 pathway and for optosis. Mass spectrometry has been used to identify these adducts, and recent studies have focused on understanding the specific proteins targeted by 4-HNE and how they affect cellular responses. This article was authored by Ledigia Malkovic, Nevan Zarkovic, Zlatko Morozyk, and others.