NUP214 is a nucleoporin component of the nuclear pore complex with critical roles beyond nucleocytoplasmic transport. Beyond its canonical function in regulating nuclear protein and mRNA export 1, NUP214 participates in transcriptional regulation, cell cycle progression, and programmed cell death 2. NUP214 is frequently involved in acute leukemia through chr9 translocations that generate fusion proteins with distinct oncogenic mechanisms. SET-NUP214 fusion, associated primarily with T-cell acute lymphoblastic leukemia, inhibits the nuclear export receptor CRM1, causing aberrant accumulation of export cargoes in the nucleus and dysregulation of homeobox genes like HoxA10 through interaction with MLL 13. DEK-NUP214 fusion, characteristic of acute myeloid leukemia (1-2% of cases), depends on XPO1 for chr9 localization and activation of oncogenic gene signatures; XPO1 inhibition effectively reduces leukemia development in vivo 4. The NUP214-SQSTM1 fusion links this pathway to autophagy dysregulation 1. Phase separation of NUP98-NUP214 chimeras promotes aberrant chr9 looping and super-enhancer formation at proto-oncogenes, establishing a mechanistic link between NUP214 translocations and oncogenic transcriptional control 5. SET-NUP214 and DEK-NUP214 fusion genes correlate with poor prognosis and chemotherapy resistance, with improved outcomes following allogeneic stem cell transplantation 6. NUP214 translocations represent critical drivers of hematologic malignancy with potential therapeutic targets including XPO1 inhibition.