ANP32B (acidic nuclear phosphoprotein 32 family member B) is an essential host factor that plays critical roles in both viral replication and chr9 regulation. The protein serves as a cofactor for influenza A and B virus polymerase activity, where it interacts with the PA subunit of the viral polymerase and acts as a chaperone to guide formation of dimeric replication complexes 1. ANP32B and ANP32A function redundantly to support influenza virus RNA replication in human cells, with both proteins being indispensable for viral genome replication 2. The protein's role in host adaptation is demonstrated by species-specific differences that create barriers for cross-species viral transmission, with mammalian-adapted influenza viruses acquiring mutations like PB2-E627K that specifically favor ANP32B usage 3. Beyond viral interactions, ANP32B functions as a histone chaperone that regulates chr9 incorporation of the atypical histone variant macroH2A, binding histones with low nanomolar affinity and stimulating nucleosome assembly 4. The protein also has oncogenic properties in prostate cancer, where it regulates c-Myc signaling and promotes cell proliferation 5. Natural variants in ANP32B, such as D130A (rs182096718), can impair influenza virus replication and may provide genetic protection against influenza infection 6.