Editing Endoplasmic reticulum (section)

==Clinical significance==
Increased and supraphysiological ER stress in pancreatic β cells disrupts normal insulin secretion, leading to hyperinsulinemia<ref>{{cite journal |last1=Yong |first1=Jing |last2=Johnson |first2=James D. |last3=Arvan |first3=Peter |last4=Han |first4=Jaeseok |last5=Kaufman |first5=Randal J. |title=Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus |journal=Nature Reviews Endocrinology |date=August 2021 |volume=17 |issue=8 |pages=455–467 |doi=10.1038/s41574-021-00510-4 |pmid=34163039 |pmc=8765009 }}</ref> and consequently peripheral insulin resistance associated with obesity in humans.<ref>{{cite journal |last1=van Vliet |first1=Stephan |last2=Koh |first2=Han-Chow E. |last3=Patterson |first3=Bruce W. |last4=Yoshino |first4=Mihoko |last5=LaForest |first5=Richard |last6=Gropler |first6=Robert J. |last7=Klein |first7=Samuel |last8=Mittendorfer |first8=Bettina |title=Obesity Is Associated With Increased Basal and Postprandial β-Cell Insulin Secretion Even in the Absence of Insulin Resistance |journal=Diabetes |date=1 October 2020 |volume=69 |issue=10 |pages=2112–2119 |doi=10.2337/db20-0377 |pmid=32651241 |pmc=7506835 }}</ref> Human clinical trials also suggested a causal link between obesity-induced increase in insulin secretion and peripheral insulin resistance.<ref>{{cite journal |last1=Mittendorfer |first1=Bettina |last2=Patterson |first2=Bruce W. |last3=Smith |first3=Gordon I. |last4=Yoshino |first4=Mihoko |last5=Klein |first5=Samuel |title=β Cell function and plasma insulin clearance in people with obesity and different glycemic status |journal=Journal of Clinical Investigation |date=1 February 2022 |volume=132 |issue=3 |pages=e154068 |doi=10.1172/JCI154068 |pmid=34905513 |pmc=8803344 }}</ref>

Abnormalities in [[XBP1]] lead to a heightened [[XBP1#Endoplasmic reticulum stress response|endoplasmic reticulum stress response]] and subsequently causes a higher susceptibility for inflammatory processes that may even contribute to [[Alzheimer's disease]].<ref name="Casas-Tinto-2011">{{cite journal | vauthors = Casas-Tinto S, Zhang Y, Sanchez-Garcia J, Gomez-Velazquez M, Rincon-Limas DE, Fernandez-Funez P | title = The ER stress factor XBP1s prevents amyloid-beta neurotoxicity | journal = Human Molecular Genetics | volume = 20 | issue = 11 | pages = 2144–60 | date = June 2011 | pmid = 21389082 | pmc = 3090193 | doi = 10.1093/hmg/ddr100 }}</ref>  In the [[Colon (anatomy)|colon]], XBP1 anomalies have been linked to the inflammatory bowel diseases including [[Crohn's disease]].<ref name="Kaser-2008">{{cite journal | vauthors = Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS | title = XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease | journal = Cell | volume = 134 | issue = 5 | pages = 743–56 | date = September 2008 | pmid = 18775308 | pmc = 2586148 | doi = 10.1016/j.cell.2008.07.021 }}</ref>

The [[unfolded protein response]] (UPR) is a [[cellular stress response]] related to the endoplasmic reticulum.<ref>{{cite web |url=https://www.ibiology.org/cell-biology/unfolded-protein-response/ |title=Peter Walter's Short Talk: Unfolding the UPR |publisher=iBiology |first=Peter |last=Walter }}</ref> The UPR is activated in response to an accumulation of unfolded or misfolded [[protein]]s in the [[Lumen (anatomy)|lumen]] of the endoplasmic reticulum. The UPR functions to restore normal function of the cell by halting protein [[translation (genetics)|translation]], degrading misfolded proteins, and activating the signaling pathways that lead to increasing the production of molecular [[Chaperone (protein)|chaperones]] involved in [[protein folding]]. Sustained overactivation of the UPR has been implicated in [[prion]] diseases as well as several other [[neurodegeneration|neurodegenerative diseases]] and the inhibition of the UPR could become a treatment for those diseases.<ref>{{cite journal | vauthors = Moreno JA, Halliday M, Molloy C, Radford H, Verity N, Axten JM, Ortori CA, Willis AE, Fischer PM, Barrett DA, Mallucci GR | title = Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice | journal = Science Translational Medicine | volume = 5 | issue = 206 | pages = 206ra138 | date = October 2013 | pmid = 24107777 | doi = 10.1126/scitranslmed.3006767 | s2cid = 25570626 }}</ref>