An impaired skin barrier can trigger skin inflammation, which in turn can weaken the barrier even further, creating a vicious cycle. However, the specific mechanisms involved in this cycle are not yet fully understood. One of them is protein citrullination, that is conversion of peptidyl-arginine into peptidyl-citrulline by peptidylarginine deiminases (PADs). Even though citrullination is critical for skin homeostasis, the precise role of PADs in skin diseases remains unclear. Our studies show that citrullination is dysregulated during skin inflammation primarily through decrease in levels of PAD1 isotype. This decrease is limited to areas of the skin affected by inflammation. Among the targets of PADs in skin, citrullination of filaggrin is crucial for maintaining the skin barrier. A linear association between PAD1 levels and filaggrin citrullination suggested that reduced filaggrin citrullination in inflamed skin may be linked to decreased PAD1 levels. When exposed to cytokines associated with inflammation such as IL-22, IL-4, and IL-13, PAD1 levels decreased in skin cells. Importantly, this negative effect could be reversed using drugs commonly used to treat skin conditions, like Vitamin D, Acitretin, and Baricitinib. Together these findings could pave the way for application of PAD inducers as alternate therapy in inflammatory skin diseases.