Misfolded proteins of the endoplasmic reticulum (ER) are moved across the ER membrane into the cytosol where they are poly-ubiquitinated and degraded by the proteasome. This process is called ER associated protein degradation (ERAD) or retrotranslocation. The mechanism of ERAD is poorly understood. In this project, we want to answer the questions of how proteins are selected for retrotranslocation and how retrotranslocation is regulated. To this end, we will combine in vitro reconstitution experiments with purified proteins and experiments in intact cells using the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe as model organisms.