We report biochemically how PLUM-EZH2 interaction leads to enhanced PRC2 activity, promoting chemoresistance via the activation of UPR pathway, in addition to several targeted therapy-based studies confirming the involvement of cross talk between UPR pathway regulators (IRE1α, eIF2α, ATF6α) in driving MM pathogenesis and chemoresistance58,59,65–70. Here, ATF6 is linked to Miyoshi myopathy.