The in vitro model of CFZ-adapted MM cells used here matches the currently known major characteristics of PI-refractory MM, such as lack of proteasome mutation and IRE1/XBP1-low stage.15, 16 Overexpression of the ABCB1 drug exporter has been observed in MM cells, including CFZ-resistant MM,16 but its functional significance was unclear. Here, XBP1 is linked to Miyoshi myopathy.