Kallikrein 5 and Kallikrein 7 (KLK5/KLK7)

Class

dual anti-KLK5/KLK7 monoclonal antibody

Pathway

protease-driven epidermal barrier dysfunction and inflammation/itch signaling in AD

Kallikrein 5 (KLK5) and kallikrein 7 (KLK7) are serine proteases produced by skin cells that normally control the shedding of the outermost skin layer (desquamation) by cleaving structural proteins that hold dead skin cells together. In healthy skin, their activity is tightly restrained by endogenous protease inhibitors. When this balance is disrupted, excess KLK5/KLK7 activity degrades the skin barrier and directly activates a receptor called protease-activated receptor 2 (PAR2) on skin and nerve cells, triggering release of inflammatory mediators and itch signals. This protease-driven cascade is a recognized contributor to atopic dermatitis and related barrier-defect skin conditions, where impaired barrier function and chronic itch reinforce each other. A dual antibody that neutralizes both KLK5 and KLK7 aims to address this pathway more completely than blocking either enzyme alone, since the two proteases have overlapping but not identical substrates and both feed into PAR2 activation and barrier breakdown. By restraining excess protease activity at its source, this approach is intended to reduce inflammatory signaling, itch, and barrier disruption together, rather than treating downstream inflammation in isolation, offering a mechanistically distinct alternative to therapies that target cytokines or their receptors further downstream in the immune cascade.