Abstract

The efficient folding of membrane and secreted proteins relies on the unfolded protein response (UPR) to buffer fluctuations in the load of misfolded proteins. Although the UPR is thought to operate on a generic manner to maintain ER proteostasis, a recent study revealed the existence of a novel mechanism to eliminate misfolded GPI-anchored proteins via the secretory pathway, termed rapid ER stress-induced export' (RESET) (Satpute-Krishnan etal, ). RESET involves the export of misfolded GPI proteins to the plasma membrane for subsequent degradation by the lysosome.