Targeting ER stress and the UPR with chemical and pharmacological drugs in metabolic diseases. TUDCA and PBA are chemical chaperones that improve protein folding in a non-specific manner. Valproate and BIX Bix are two small molecules, BIP Bip inducers. Verapamil is a calcium channel blocker, which includes the calcium release channel IP3R. CDN1163 is a small allosteric activator of SERCA2b. GSK2606414 and GSK2656157 are PERK inhibtors. Salubrinal is a small molecule, which reduces dephosphorylation of eIF2α. Ursolic acid and tomatidine are inhibitors of ATF4. SB203580 is a specific inhibitor of the p38 MAP kinase, which phosphorylates CHOP. STF-083010 and 4µ8C are inhibitors of IRE1 RNase activity. The small molecule 2-[5-[1-(4-chlorophenoxy)ethyl]-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide (TSPA) is a small allosteric activator, which functions as an ATF6α translocation inducer. Abbreviations: inositol 1,4,5-trisphosphate(IP3R) receptorIP3R (inositol 1,4,5-trisphosphate) receptor. Grey boxes contain the name of the drugs (sharp arrows, activators; bar-ended arrows, inhibitors).