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Review

Nature Cell Biology 7, 766–772 (1 August 2005) | doi:10.1038/ncb0805-766

ERAD: the long road to destruction

Birgit Meusser , Christian Hirsch , Ernst Jarosch & Thomas Sommer

Endoplasmic reticulum (ER)-associated protein degradation (ERAD) eliminates misfolded or unassembled proteins from the ER. ERAD targets are selected by a quality control system within the ER lumen and are ultimately destroyed by the cytoplasmic ubiquitin–proteasome system (UPS). The spatial separation between substrate selection and degradation in ERAD requires substrate transport from the ER to the cytoplasm by a process termed dislocation. In this review, we will summarize advances in various aspects of ERAD and discuss new findings on how substrate dislocation is achieved.