Herein, we found that knockdown of Poldip2 effectively reduced protein levels of p-IKKα/β, p-IκBα, and p-P65 but enhanced protein level of IκBα in ALI mice, suggesting that the protective effects of Poldip2 knockdown in alleviating LPS-induced inflammation may be in relation to NF-κB signaling inactivation. Here, NFKBIA is linked to acute respiratory distress syndrome.