Protein dislocation from the ER

► Misfolded proteins of the secretory pathway are degraded by cytosolic proteasomes. ► Proteolysis of such molecules is preceded by their removal from the endoplasmic reticulum (ER). ► Key players in this process are multimeric ubiquitin ligases that are integrated into the ER membrane. ► These ligase complexes partake in the selection and polyubiquitylation of substrates and may also contribute to the formation of dynamic channels for protein export.