NUP98 (nucleoporin 98 and 96 precursor) is a nuclear pore complex component that becomes oncogenic when disrupted by chr11 translocations in hematologic malignancies. Wild-type NUP98 functions as a structural component of nuclear pores, but NUP98 fusion oncoproteins retain the intrinsically disordered N-terminal region containing phenylalanine-glycine repeats that drive liquid-liquid phase separation (LLPS) 12. These fusion proteins form nuclear condensates that are essential for leukemic transformation by enhancing chr11 occupancy, creating super-enhancer-like binding patterns, and inducing CTCF-independent chr11 loops at proto-oncogenes 1. NUP98 fusions occur in approximately 7.2% of pediatric acute myeloid leukemia cases, with NUP98-NSD1 and NUP98-KDM5A being most prevalent, and are associated with poor prognosis 3. The oncogenic mechanism involves hijacking the KMT2A-MENIN complex and antagonizing polycomb repressive complexes to maintain pro-leukemogenic gene expression 4. Phase separation is critical for transformation, as artificial fusion proteins with unrelated LLPS-forming domains can recapitulate oncogenic effects 1. Therapeutically, NUP98-rearranged leukemias show vulnerability to menin inhibitors and MYST histone acetyltransferase inhibitors 5, representing promising precision medicine approaches for these high-risk pediatric malignancies 6.