Quality control at the plasma membrane: One mechanism does not fit all

The plasma membrane quality control system of eukaryotic cells is able to recognize and degrade damaged cell surface proteins. Recent studies have identified two mechanisms involved in the recognition of unfolded transmembrane proteins. One system uses chaperones to detect unfolded cytoplasmic domains of transmembrane proteins, whereas the second mechanism relies on an internal quality control system of the protein, which can trigger degradation when the protein deviates from the folded state. Both quality control mechanisms are key to prevent proteotoxic effects at the cell surface and to ensure cell integrity.