Kallikrein-related peptidase (KLK)

Epidermal kallikreins, primarily comprising kallikrein-related peptidases 5 (KLK5), 7 (KLK7), and 14 (KLK14), are a group of serine proteases essential for skin homeostasis and barrier function (Kishibe, 2018). These enzymes are secreted into the extracellular space of the stratum corneum, where they catalyze the degradation of corneodesmosomes to facilitate natural skin shedding, a process known as desquamation (Hovnanian, 2013). Under physiological conditions, their activity is tightly regulated by endogenous inhibitors like the lympho-epithelial Kazal-type-related inhibitor (LEKTI); however, a deficiency in these inhibitors leads to uncontrolled proteolysis (UniProt Consortium, 2024). This dysregulation is a primary driver of Netherton syndrome and contributes significantly to the pathogenesis of atopic dermatitis and rosacea by promoting skin barrier breakdown and triggering pro-inflammatory signaling via protease-activated receptor 2 (PAR2) (Kishibe, 2018). Consequently, these enzymes are major therapeutic targets, with drug development focusing on topical inhibitors and replacement therapies to restore the proteolytic balance in the skin (Hovnanian, 2013).

Other names

Epidermal kallikreinsTissue kallikreinsStratum corneum chymotryptic enzyme (KLK7)Stratum corneum tryptic enzyme (KLK5)Kallikrein-5Kallikrein-7Kallikrein-14

Inhibition of serine protease activity to prevent the premature degradation of corneodesmosomal proteins and the activation of pro-inflammatory signaling pathways via protease-activated receptor 2 (PAR2).