Endoplasmic reticulum (ER) is an important intracellular organelle responsible for modifying and folding newly synthesized secretory and membrane proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress. A key player in the cellular stress response is in the ER. The ER provides quality control system to refold and/or degrade misfolded proteins. The unfolded protein response, however, can trigger cell death if ER dysfunction is severe or prolonged. It is thought that the ER stress is associated with the pathogenesis of type 2 diabetes. Because the islet amyloid polypeptide in beta cells undergoes a change in tertiary structure followed by self-association and tissue deposition, which eventually causes beta cell dysfunction, type 2 diabetes is also defined as a conformational disease.