Robert Ernst1,2, Mike F. Renne1,2, Aamna Jain1,2 and Alexander von der Malsburg1,2 1Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland University, 66421 Homburg, Germany 2Preclinical Center for Molecular Signaling (PZMS), Medical Faculty, Saarland University, 66421 Homburg, Germany Correspondence: robert.ernstuks.eu

The endoplasmic reticulum (ER) is the key organelle for membrane biogenesis. Most lipids are synthesized in the ER, and most membrane proteins are first inserted into the ER membrane before they are transported to their target organelle. The composition and properties of the ER membrane must be carefully controlled to provide a suitable environment for the insertion and folding of membrane proteins. The unfolded protein response (UPR) is a powerful signaling pathway that balances protein and lipid production in the ER. Here, we summarize our current knowledge of how aberrant compositions of the ER membrane, referred to as lipid bilayer stress, trigger the UPR.