The role of kallikreins in inflammatory skin disorders and their potential as therapeutic targets

The skin is a vital organ of the human body, serving numerous protective and functional roles that are essential for survival. Residing in the epidermis are various epidermal proteases responsible for the establishment and regulation of barrier function. The human tissue kallikrein-related peptidase family conserves homeostasis of the skin barrier through their roles in desquamation, antimicrobial defense, innate immune response, and barrier maintenance. The activity of kallikreins is tightly regulated and dysregulation of kallikrein activity is seen to contribute to the formation of several inflammatory skin disorders. This review highlights the roles of kallikreins in skin homeostasis and pathologies. Due to their part in these skin disorders, inhibitors of the skin kallikreins have become attractive therapeutics. Over the past few years, both natural and synthetic inhibitors of several kallikreins have been identified and are undergoing further development as treatments to restore compromised barrier function. This review summarizes the kallikrein inhibitors under development for this purpose. These inhibitors remain promising therapeutics in cases of severe skin inflammation not well managed by current therapies.