It's all about your contacts: Membrane contact sites have recently come to the fore of our understanding of interorganelle communication. Wuet al.review how these important structures help to promote a variety of key functions, including organelle division and lipid transfer. Focusing on contacts between the endoplasmic reticulum and a variety of organelles or the plasma membrane reveals the generality and importance of these contacts in cellular homeostasis and organismal health.Science, this issue p.eaan5835

Even with the assistance of many cellular factors, a significant fraction of newly synthesized proteins ends up misfolded. Cells evolved protein quality control systems to ensure that these potentially toxic species are detected and eliminated. The best characterized of these pathways, the ER-associated protein degradation (ERAD), monitors the folding of membrane and secretory proteins whose biogenesis takes place in the endoplasmic reticulum (ER). There is also increasing evidence that ERAD controls other ER-related functions through regulated degradation of certain folded ER proteins, further highlighting the role of ERAD in cellular homeostasis.