NPM1 encodes a multifunctional nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm to regulate diverse cellular processes. It acts as a histone chaperone and nucleic acid-binding protein involved in ribosome biogenesis, centrosome duplication, DNA repair, and cell cycle control. NPM1 also negatively regulates apoptosis and antagonizes ATF5-induced cell cycle arrest, while enhancing transcription of MYC target genes in cooperation with MYC. NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia, occurring in approximately 30% of de novo cases 1. These mutations cause aberrant cytoplasmic dislocation of the NPM1 protein, leading to dysregulated HOX/MEIS gene expression that drives leukemic cell survival 2. Beyond AML, NPM1 overexpression in solid tumors promotes immune evasion by sequestering the transcription factor IRF1 from MHC-I and MHC-II promoters, thereby suppressing antigen presentation 3. In breast cancer, hypoxia-induced NPM1 upregulation increases PD-L1 expression and inhibits T cell infiltration 4. NPM1-mutated AML is recognized as a distinct entity in WHO classification. Recent therapeutic approaches include BH3 mimetics and menin-MLL interaction inhibitors, which show exquisite leukemic cell toxicity in preclinical models and clinical efficacy 2. Neoantigen-targeted immunotherapies against mutant NPM1 are also under development 5.