Taylor and colleagues found that recurrent and lineage-specific mutations in exportin-1 (XPO1)—the protein predominantly responsible for nuclear export of proteins 40 kDa and larger—change how proteins are distributed in the nucleus and cytoplasm. These mutations also increased tumor growth in mouse xenotransplantation experiments and promoted oncogenesis in a conditional knock-in mouse model. Altered protein export was also observed in a B-cell precursor leukemia cell line; some differentially exported proteins included participants in the K63-ubiquitination, TLR4, and NFκB pathways. Both in vitro and in vivo, the tested XPO1 mutation caused increased sensitivity to treatment with selinexor, an XPO1 inhibitor. For details, please see the article by Taylor and colleagues on page 1452.