XPO1 (exportin 1) is a nuclear export protein that mediates the transport of proteins and RNAs from the nucleus to the cytoplasm, playing a crucial role in cellular homeostasis 1. As a karyopherin, XPO1 recognizes nuclear export signals on cargo molecules and facilitates their passage through nuclear pore complexes 1. XPO1 has specialized functions in viral biology, mediating export of unspliced RNAs from viruses including HIV-1 and influenza A, and facilitating nuclear export of viral regulatory proteins 2. In cancer biology, dysregulation of XPO1 is pivotal in developing solid and hematological malignancies and contributes to therapy resistance 2. In NPM1-mutated acute myeloid leukemia, XPO1 maintains cytoplasmic localization of mutant NPM1, which sustains the leukemic state through HOX gene expression; XPO1 inhibition relocalizes NPM1c to the nucleus and promotes differentiation 3. XPO1 inhibitors, particularly selinexor (KPT-330), have been clinically validated, with FDA approval for multiple myeloma and diffuse large B cell lymphoma 2. Selinexor shows therapeutic promise in combination approaches: with CDK4/6 inhibitors in liver cancer 4, with MDM2 inhibitors to reactivate p53 in AML 5, and with gemcitabine-nab-paclitaxel in pancreatic cancer 6. These findings establish XPO1 as a critical vulnerability in multiple cancer types.