Glucose on the sugar side chains of proteins keeps unfolded proteins in the ER. Mannoses on sugar side chains act as a timer for protein folding. Unfolded proteins in the ER are threaded through a retrotranslocon into the cytosol where they are ubiquitylated and digested. IRE1, ATF6 and PERK sense the amount of unfolded protein and generates several responses to reduce the effects and amount of unfolded protein.