ANP32A is an essential host factor that mediates influenza virus genome replication through a mechanism involving viral polymerase assembly. Structurally, ANP32A's N-terminal leucine-rich repeat domain bridges two viral RNA polymerase (FluPol) molecules into an asymmetric dimer, while its C-terminal low-complexity acidic region inserts between the juxtaposed PB2 627 domains of the polymerase 1. This dimeric complex serves as a replication platform for viral RNA genome synthesis 1. ANP32A is critical for influenza A, B, and C virus replication 2, and plays an essential role in foamy virus mRNA export from the nucleus. Species-specific sequence differences in ANP32A—notably a 33-amino acid insertion in avian versus mammalian forms—create a major host-restriction barrier limiting zoonotic transmission of avian influenza viruses to mammals 3. Adaptive mutations in the viral polymerase, particularly PB2-E627K, enable avian viruses to overcome this restriction by facilitating efficient interaction with mammalian ANP32A 3. ANP32A itself is subject to post-translational modification; SUMOylation of human ANP32A by PIAS2α recruits the viral NS2 protein, which further enhances polymerase-ANP32A interactions and promotes viral replication 4. Beyond viral infection, ANP32A is abundantly expressed in the developing mammalian brain, particularly in the cerebellum and cerebral cortex, suggesting roles in neuronal differentiation 5.