Endoplasmic reticulum stress and the on site function of resident PTP1B

► In the UPR adaptive response to ER stress, PTP1B uses PERK as substrate. ► The chronic ER stress conducts to insulin and leptin resistance. ► PTP1B negatively regulates ER stress, as well as insulin and leptin resistance. ► PTP1B inhibitors have the potential to alleviate ER stress in diabetes mellitus.