Coupled with a deficiency of sRAGE (67), increased levels of S100A12 in the airways interact with RAGE, followed by activation of the p38 MAPK pathway in neutrophils leading to the continuous release of pro-inflammatory mediators, contributing to chronic inflammation, worsening CF progression, and impaired lung function (11, 67, 68). This evidence concerns the gene AGER and cystic fibrosis.