Response categories of the Unfolded Protein Response. Three ER transmembrane proteins, IRE1, PERK, and ATF6, sense ER stress in the ER lumen and become activated regulating a cascade of signaling pathways collectively termed the Unfolded Protein Response (UPR). The UPR has three functions: adaptive response, feedback control, and cell fate. Under the adaptive response, the UPR aims to reduce ER stress and restore ER homeostasis. If the UPR is successful, the UPR signaling pathways are turned off by feedback mechanisms. The UPR also regulates both survival and death factors that govern whether the cell will live or not depending on the severity of the ER stress condition.