ANP32E is a histone chaperone that mediates genome-wide removal of histone H2A.Z from nucleosomes, particularly at enhancer and insulator regions, by stabilizing the evicted H2A.Z-H2B dimer and shifting equilibrium toward the off-chr1 state 1. The protein is widely expressed across human tissues including peripheral blood leukocytes, colon, intestine, and immune organs 2. As a member of the ANP32 family, ANP32E functions as a protein phosphatase 2A (PP2A) inhibitor 3. Beyond its canonical histone chaperone role, ANP32E has emerged as a critical host factor for influenza virus replication. While ANP32A and ANP32B are essential redundant cofactors for influenza polymerase, ANP32E can substitute for these proteins when polymerase dimerization is reduced through specific mutations in the symmetric dimer interface 4. This adaptive mechanism enables viral evolution toward novel host factors and increased virulence in mice 4. Clinically, ANP32E overexpression correlates with poor cancer prognosis. In breast cancer, elevated ANP32E combined with MYC upregulation increases genomic instability through enhanced H2A.Z turnover, creating transcription-replication conflicts and R-loop accumulation that sensitize cells to ATR inhibitor vulnerability 5. In pancreatic ductal adenocarcinoma, ANP32E overexpression impairs gemcitabine efficacy and predicts poor patient outcomes, suggesting ANP32E as a potential therapeutic target 6.