Kallikrein-related peptidases and elastase 2 (KLKs/ELA2)

Kallikrein-related peptidases (KLKs) and elastase 2 (ELA2) are a group of secreted serine proteases that are essential for maintaining skin barrier integrity through the regulation of desquamation [1][2]. In healthy skin, these enzymes, particularly KLK5, KLK7, and KLK14, facilitate the shedding of dead skin cells by degrading corneodesmosomes, while ELA2 contributes to inflammatory signaling and matrix remodeling [3]. Their activity is naturally balanced by the endogenous inhibitor LEKTI; however, a deficiency in LEKTI (as seen in Netherton syndrome) leads to the uncontrolled hyperactivation of these proteases [3][4]. This overactivity causes premature skin barrier breakdown, severe dehydration, and the induction of a robust pro-inflammatory response via the IL-36 pathway [2][5]. Consequently, this protease cluster is a primary therapeutic target for rare and common inflammatory skin conditions [4]. Pharmacological agents like S0111 are designed to inhibit these enzymes simultaneously to restore the skin's protective barrier and alleviate chronic inflammation [6].

Other names

Kallikrein familyNeutrophil elastaseELANELEKTI targetsSerine proteases of the skinDesquamatory serine proteases

Inhibition of serine protease activity to prevent the premature degradation of corneodesmosomes and the activation of pro-inflammatory cytokine pathways.