4-hydroxynonenal (4-HNE) is a toxic breakdown product of damaged fatty acids that is thought to contribute to cell death. Ben Cravatt's lab has now used a variation of their previously reported cysteine-reactivity profiling assay to identify novel targets of 4-HNE reactivity, including the kinase ZAK. Interestingly, the 'HNE-ylation' of ZAK impacts the response of cancer cells to oxidative stress. They don't talk about it in the paper, but interestingly two other prominent targets of HNE modification are involved in 1-carbon metabolism, including the oncogene PHGDH. Could be an interesting link here.