Conditions that require sustained high levels of insulin production, such as hyperglycaemia, can result in the accumulation of unfolded proteins in the ER, since the bulk of chaperones necessary to prevent protein misfolding does not suffice protein synthesis so that this unbalanced situation triggers ER stress and, consequently, the unfolded protein response (UPR) in β-cells [117]. The gene discussed is INS; the disease is Hyperglycemia.