Endoplasmic reticulum stress (ER stress)

Endoplasmic reticulum stress refers to a cellular condition where the endoplasmic reticulum (ER) experiences an accumulation of misfolded or unfolded proteins due to disturbances in its homeostasis[6][9]. This triggers the unfolded protein response (UPR), a protective mechanism that attempts to restore normal function by halting general protein synthesis and upregulating chaperones for proper folding. If unresolved, chronic ER stress can lead to cell death via apoptosis and is implicated in various diseases including cancer, neurodegenerative disorders, diabetes mellitus, fatty liver disease, and inflammatory conditions[2][5][7]. While "endoplasmic reticulum stress" describes a pathophysiological state rather than a discrete molecular target such as a receptor or enzyme—and thus is not considered a canonical therapeutic target—it remains an important focus for drug discovery efforts aimed at modulating the UPR pathway or alleviating cellular dysfunction associated with chronic ER stress[2][5]. **Note:** "Endoplasmic reticulum stress" is not itself a molecule or receptor but rather describes a cellular process/state. Therefore it does not fit standard definitions of drug targets like receptors or enzymes; instead individual components of the UPR pathway (such as IRE1α/ERN1, PERK/EIF2AK3) are considered actionable targets within this context.

Other names

ER stressERSunfolded protein response (UPR)-related stress