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Understanding the interplay between the proteasome pathway and autophagy in response to dual PI3K/mTOR inhibition in myeloma cells is essential for their effective clinical application Leukemia (2013) 27, 2397–2403; doi:10.1038/leu.2013.150 In order to maintain cellular homeostasis, excess or misfolded proteins must be removed and/or recycled.1 In myeloma, plasma cells produce large quantities of immunoglobulin, and excess unfolded immunoglobulin results in high levels of endoplasmic reticulum (ER) stress. These proteins are removed either via the proteasome2 or via autophagy,3 suggesting that these pathways may be specifically exploited therapeutically. Although proteasome inhibition has been extensively explored as a therapeutic option in myeloma, little work has been performed on targeting the pathways leading to autophagy. We have previously demonstrated the importance of the unfolded protein response (UPR) in dealin