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The endoplasmic reticulum (ER) is a structure found within the cytoplasm of eukaryotic cells. Its composition has two components: the smooth endoplasmic reticulum (SER) and the rough endoplasmic reticulum (RER). The SER is generally used for the creation/ storage of lipids and steroids, while the RER plays a significant role in the synthesis of various proteins. The RER is termed "rough" due ribosomal attachments to the surface compared to the SER, which does not have ribosomes.

Unfolded or misfolded proteins remain in the ER, translocated to the cytoplasm by ER-associated protein degradation (ERAD), and then degraded by the proteasome. The amount of unfolded proteins can accumulate to the extent where it exceeds the capacity of ERAD machinery to dispose of it all. This accumulation leads to ER stress in the cell. Three pathways that regulate the mammalian ER stress response are PERK (translational attenuation), ATF6 (enhanced expression of ER chaperones), and IRE1 (enhanced expression of ERAD components).[8] Collectively, these pathways work to reduce the amount of unfolded proteins within the ER. Unfolded proteins have exposed hydrophobic amino-acid residues that are normally inside the protein. This arrangement can allow the formation of protein aggregates that are toxic to cells. If the three pathways can’t suppress ER stress, it induces an apoptotic pathway to help ensure the survival of the organism. The most characterized pathway of this by mechanism is the CHOP pathway, but other apoptotic pathways that can be activated as well.[8] A few of these pathways include the IRE1-TRAF2-ASK1 pathway, caspases, Bcl2 proteins, and c-Abl activation by death signals.