eIF2α phosphorylation is an emerging therapeutic target for a broad range of diseases, from cancer to neurodegeneration.53,54 In previous work, we discovered inhibitors of R15A (Guanabenz and Sephin1) and R15B (Raphin1).30,55–57 Guanabenz and Sephin1 have recently entered the clinic with Guanabenz showing efficacy in a phase 2 clinical trial for ALS,58 and Sephin1 has successfully gone through a phase 1 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03610334). Here, EIF2A is linked to amyotrophic lateral sclerosis.