In contrast to PERK inhibition, although PERK knockdown suppressed the expression of ATF4 as well as of total and phosphorylated EIF2α, it differentially affected the expression levels of ATF6 and XBP1 in the two MM cell lines assayed, indicating a differential mechanism of action in the supporting branches of the UPR such as IRE1 and ATF6. This evidence concerns the gene EIF2AK3 and Miyoshi myopathy.