L-2-Hydroxyglutaric acid (L-2-HG) is a compartmentalized metabolite and a substrate for L-2-hydroxyglutarate dehydrogenase (L2HGDH). It inhibits histone demethylases and increases the expression of ATF4 and its target genes by activating the mTOR pathway. L-2-Hydroxyglutaric acid mediates the mTOR-ATF4 signaling pathway and can be used in biosensor research.