This EMBO Workshop will include new discoveries that surround the ER's historical and important role in regulating the translation, translocation and folding of membrane and secreted proteins of the secretory pathway. It will further include new insights into the signaling pathways that allow the ER to correct for cell stress, the unfolded protein response, and maintaining lipid homeostasis. Recent years have also revealed emerging and unexpected new functions for this old organelle in regulating the biogenesis of other organelles at membrane contact sites (MCSs). These MCSs have generated much excitement in cell biology because they are hybrid locations where the elaborate ER network can communicate with other organelles through calcium signaling, lipid metabolism, and the recruitment of machineries that modify membrane shape, trafficking and division. They reveal that not every membrane bound component traffics through vesicles, rather many move directly at positions where the ER is tethered and apposed to the plasma membrane and other organelles to rapidly communicate signals across the cell that can maintain homeostasis. Disruption of ER homeostasis and ER structure is a hallmark of various diseases. Thus, understanding basic mechanisms controlling ER functions may provide insight into a broad range of pathologies.