To our surprise, CALR variants were found to be faintly expressed in cells, in part because of an excessive secretion associated with the loss of the KDEL motif, but also due to a catabolic process mainly mediated by the ERAD-proteasome system, thus allowing us to believe that MPN-associated CALR variants might indeed be considered as improperly folded proteins. Here, CALR is linked to myeloproliferative neoplasm.