RESET ing ER proteostasis: selective stress pathway hidden in the secretory route

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 et al , [Satpute‐Krishnan P, 2014]). RESET involves the export of misfolded GPI proteins to the plasma membrane for subsequent degradation by the lysosome.