Furthermore, we identified a new small molecule by using cell-based screening that phosphorylates eIF2α and regulates downstream target genes related to amino acid metabolism as well as Fgf21. Collectively, our findings suggest that eIF2α phosphorylation in skeletal muscle cells control cell autonomous and non–cell-autonomous metabolic regulation, providing potential therapeutic targets for metabolic diseases. Here, EIF2A is linked to Other metabolic disease.