The functional integrity of NPM1 is dependent on its ability to shuttle between the nucleus and cytoplasm, and this ability is severely compromised in NPM1 mutated AML.11 The mutations (termed NPM1c mutations) uniformly alter one or both critical tryptophan residues in the C-terminus of the protein, which prevent proper folding12 and destroys a nucleolar localization signal. Here, NPM1 is linked to acute myeloid leukemia.