NPM1 (nucleophosmin 1) is the most abundant nucleolar protein that shuttles between nucleus and cytoplasm, performing diverse cellular functions critical for cell homeostasis 1. Primary functions include ribosome biogenesis and nuclear export, histone chaperoning for core histones H3, H2B, and H4, centrosome duplication regulation in cooperation with BRCA2, and DNA repair coordination 1. NPM1 negatively regulates apoptosis through inhibition of EIF2AK2/PKR autophosphorylation and antagonizes ATF5-mediated G2/M blockade, thereby promoting cell proliferation 1. The protein participates in liquid-liquid phase separation for nucleolus formation and responds to nucleolar stress 1. Clinically, NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia (AML), occurring in approximately one-third of cases and conferring a more favorable prognosis 2. Mutant NPM1 undergoes C-terminal changes causing pathological cytoplasmic delocalization rather than normal nucleolar localization 1. NPM1-mutated AML is recognized as a distinct WHO-classified entity with unique biological features 2. Beyond AML, high NPM1 expression predicts poor survival across various human tumors through suppression of antigen presentation; mechanistically, NPM1 sequesters transcription factor IRF1 from MHC-I and MHC-II promoters, promoting immune evasion 3. Emerging therapies targeting NPM1-mutated AML include menin inhibitors and XPO1 inhibitors 2.