The endoplasmic reticulum (ER) is the port of entry of membrane and secretory proteins into the central vacuolar system, which includes the ER itself, the Golgi apparatus, lysosomes, endosomes, the plasma membrane, and intermediate transport compartments. The ER is also the site where nascent secretory and membrane proteins acquire their mature tertiary and quaternary structures.“Quality control” mechanisms in the ER ensure that nascent proteins that fail to fold or to oligomerize correctly are not deployed to distal compartments of the secretory pathway and, following a lag period of variable duration, are rapidly degraded (reviewed by