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Two years ago, a small molecule was discovered that enhanced the memory of rodents (1). Pinpointing the target of this compound, called integrated stress response inhibitor (ISRIB), could guide the development of cognitive disorder treatments. Two groups have now identified a target. On page 1027 of this issue, Sekine et al. (2) report, as do Sidrauski et al. (3), that ISRIB increases the activity of eukaryotic translation initiation factor 2B (eIF2B), a factor that regulates protein synthesis in a pathway underlying the cellular response to stress.