Citrullination, a unique form of posttranslational modification of proteins, is catalyzed by peptidylarginine deiminases (PADs). Recent studies have clearly demonstrated that citrullination critically regulates the function of immune cells, such as neutrophils, macrophages, and lymphocyte. However, it remains elusive as to whether citrullination also intrinsically regulates the function of non-immune cells, such as fibroblasts, which are the major source of extracellular matrix, and can functionally interact with immune cells. This talk will present data showing how unbiased multi-omic approaches lead to the discoveries of unexpected roles of PAD2 in regulating the formation of elastic fibers and the development of interstitial lung diseases/fibrosis through lung fibroblasts. In addition, the potential impacts of PADs through fibroblasts on emphysema and oncogenesis will be discussed. The audience is expected to gain a global view of how dysregulated citrullination in fibroblasts may contribute to the development of many human diseases.