CALR and myeloproliferative neoplasm: Studies focusing on the mechanism of CALR-mutated MPN have shown that these two types of CALR mutants display differential loss of function, as type 1 CALR loses its Ca2+-binding activity which leads to activation of IRE1α-XBP1 pathway of the unfolded protein response (UPR) [10], whereas type 2 CALR loses its molecular chaperone ability, which results in activation of independency on ATF6 pathway of the UPR [11].