Proteins that are translocated into the endoplasmic reticulum (ER) undergo quality control so that only correctly folded proteins are moved on in the secretory pathway. If a protein cannot reach its native folded state, it is ultimately transported back into the cytosol, poly-ubiquitinated, and degraded by the proteasome, a process called ER-associated protein degradation (ERAD). How proteins are retro-translocated across the ER membrane and moved into the cytosol is only poorly understood. Previous work demonstrated that the ubiquitin ligase Hrd1p is the only membrane component needed for a basic ERAD process. Now, the Rapoport group shows that key steps of basic ERAD can be recapitulated with purified components (Stein et al., Cell 158, 1375-1388). Hrd1p binds misfolded protein substrates, discriminating them from folded proteins. Subsequently, both Hrd1p and substrate are poly-ubiquitinated. Next, the Cdc48p ATPase complex binds and uses the energy of ATP hydrolysis to release substrate from Hrd1p. Finally, ubiquitin chains are trimmed by the de-ubiquitinating enzyme Otu1p, which is recruited and activated by the Cdc48p complex. The Cdc48-dependent extraction of poly-ubiquitinated proteins from the membrane can be reproduced with reconstituted proteoliposomes. These results provide a major step forward towards the goal to recapitulate ERAD with purified components and to elucidate the molecular mechanism of the process.