One of the best-studied ubiquitin ligases involved in protein quality control is the HMG-CoA reductase degradation-(HRD-) ligase. It is embedded in the endoplasmic reticulum (ER) membrane and constitutes the central component of a process termed ER-Associated Protein Degradation (ERAD). We want to investigate the interaction of the main components of this Module with misfolded client proteins and with the folding machinery of the ER. Besides biochemical in vitro studies and yeast genetics, this includes cryoEM and a CLMS approach.