The non-structural (NS1) protein of influenza A viruses is a multifunctional factor that plays a crucial role in modulating viral replication and host immune responses. NS1 inhibits host immune responses, particularly the production of interferons (IFNs) and the antiviral effects of IFN-induced proteins such as PKR and OAS/RNase L. Additionally, NS1 regulates viral RNA replication, viral protein synthesis, and cellular physiology. The protein is synthesized at high levels in infected cells and has a strain-specific length of 230-237 amino acids. It consists of an N-terminal RNA-binding domain and a C-terminal effector domain, which mediates interactions with host-cell proteins. NS1 localizes to the nucleus and cytoplasm, with nuclear localization sequences (NLS) facilitating its nuclear import. The protein inhibits the splicing of viral mRNA segments and enhances viral mRNA translation. It also limits IFN-β production by blocking pre-transcriptional and post-transcriptional processes. NS1 interacts with RIG-I to prevent IRF-3 activation and inhibits the processing of IFN-β pre-mRNAs. Furthermore, NS1 blocks the activity of PKR and OAS, and may antagonize the host RNAi pathway. In the adaptive immune response, NS1 suppresses dendritic cell maturation and cytokine production. Lastly, NS1 activates the PI3K pathway, which may contribute to anti-apoptotic functions during infection. These multifunctional roles of NS1 highlight its importance in the pathogenesis of influenza A viruses.The non-structural (NS1) protein of influenza A viruses is a multifunctional factor that plays a crucial role in modulating viral replication and host immune responses. NS1 inhibits host immune responses, particularly the production of interferons (IFNs) and the antiviral effects of IFN-induced proteins such as PKR and OAS/RNase L. Additionally, NS1 regulates viral RNA replication, viral protein synthesis, and cellular physiology. The protein is synthesized at high levels in infected cells and has a strain-specific length of 230-237 amino acids. It consists of an N-terminal RNA-binding domain and a C-terminal effector domain, which mediates interactions with host-cell proteins. NS1 localizes to the nucleus and cytoplasm, with nuclear localization sequences (NLS) facilitating its nuclear import. The protein inhibits the splicing of viral mRNA segments and enhances viral mRNA translation. It also limits IFN-β production by blocking pre-transcriptional and post-transcriptional processes. NS1 interacts with RIG-I to prevent IRF-3 activation and inhibits the processing of IFN-β pre-mRNAs. Furthermore, NS1 blocks the activity of PKR and OAS, and may antagonize the host RNAi pathway. In the adaptive immune response, NS1 suppresses dendritic cell maturation and cytokine production. Lastly, NS1 activates the PI3K pathway, which may contribute to anti-apoptotic functions during infection. These multifunctional roles of NS1 highlight its importance in the pathogenesis of influenza A viruses.