Mutated CALR: tails from the crypt

The discovery by exome sequencing that calreticulin (CALR) gene mutations are important gain-of-function myeloproliferative neoplasm (MPN) driver mutations(1,2) was as inexplicable as it was unexpected. In this issue of Blood, Pecquet et al(3) report that mutated CALR behaves like a rogue chaperone, usurping the role of JAK2 and promiscuously transporting immature or trafficdefective thrombopoietin receptors (TpoRs) to the cell surface from the endoplasmic reticulum (ER) (see figure).