Secretory cargo that cannot fold properly in the ER are selectively targeted for removal by a well-studied ER-associated degradation pathway, or ERAD. In contrast, very little is known about post-ER quality control mechanisms for damaged or misfolded integral membrane proteins. Here we describe a quality control function of the Rsp5-ART ubiquitin ligase adaptor network that functions to protect plasma membrane (PM) integrity. Failure to mediate this protective response during heat stress leads to toxic accumulation of misfolded integral membrane proteins at the cell surface, which causes loss of PM integrity and cell death. Thus, the Rsp5-ART network comprises a PM quality control system that works together with sequential quality control pathways in the ER and Golgi to (i) target the degradation of proteins that have exceeded their functional lifetime due to damage and/or misfolding and (ii) limit the toxic accumulation of specific proteins at the cell surface during proteotoxic stress. DOI: http://dx.doi.org/10.7554/eLife.00459.001, eLife digest Cells have evolved elaborate mechanisms for the detection of misfolded or damaged proteins, and for targeting their degradation. Since the accumulation of misfolded proteins is toxic to the cell, these protein quality control systems are critical for the maintenance of normal cellular function over the lifetime of an organism. The breakdown of this quality control correlates with the progression of neurodegenerative disorders including Alzheimer's, Huntington's and Parkinson's disease. Normal function of the protein quality control machinery can also cause disease: this is the case with channelopathies such as cystic fibrosis, in which mutant ion channels are targeted for degradation and therefore cannot function correctly at the cell surface. Understanding how protein quality control systems recognize misfolded proteins and target their degradation, and designing ways to stabilize or destabilize specific targets, particularly at the cell surface, could thus lead to the development of new therapeutic strategies. While protein quality control mechanisms in the cytosol and endoplasmic reticulum (ER) have been studied extensively, much less is known about quality control of integral membrane proteins after they exit the ER. Maintaining the quality of cell surface proteins impacts many critical biological functions including nutrient uptake, signaling and the functioning of specialized surface structures such as cell junctions. Here, Zhao et al. describe a new quality control mechanism that prevents misfolded proteins from accumulating in the plasma membrane. Building upon earlier work describing a network of adaptor proteins (called ARTs) for the Rsp5 ubiquitin ligase, Zhao et al. show that subjecting cells to proteotoxic stress, particularly thermal stress, triggers ART-Rsp5-mediated clearance of misfolded plasma membrane proteins. When ART-Rsp5-mediated clearance is abrogated, misfolded proteins accumulate at the cell surface, resulting in a rapid loss of cellular integrity. In the brain, such proteotoxicity can lead to cell death and neurodegeneration, thereby highlighting the importance of this plasma membrane quality control system. DOI: http://dx.doi.org/10.7554/eLife.00459.002