The endoplasmic reticulum: A hub of protein quality control in health and disease

One third of the eukaryotic proteome is synthesized at the endoplasmic reticulum (ER), whose unique properties provide a folding environment substantially different from the cytosol. A healthy, balanced proteome in the ER is maintained by a network of factors referred to as the ER quality control (ERQC) machinery. This network consists of various protein folding chaperones and modifying enzymes, and is regulated by stress response pathways that prevent the build-up as well as the secretion of potentially toxic and aggregation-prone misfolded protein species. Here, we describe the components of the ERQC machinery, investigate their response to different forms of stress, and discuss the consequences of ERQC break-down.