MPL and myeloproliferative disorder: Mutations affecting exon 9 of the CALR gene lead to the generation of a C-terminally modified CALR protein that lacks the KDEL endoplasmic reticulum (ER) retention signal and consequently mislocalizes outside of the ER where it activates the thrombopoietin receptor in a cell-autonomous fashion, thus driving myeloproliferative diseases.