Kallikrein-related peptidase 5 (KLK5) and Kallikrein-related peptidase 7 (KLK7) (KLK5/KLK7)

The pH-dependent desquamatory enzymes in the stratum corneum, primarily Kallikrein-related peptidase 5 (KLK5) and Kallikrein-related peptidase 7 (KLK7), are essential serine proteases responsible for the controlled shedding of dead skin cells known as corneocytes (Caubet et al., 2004, J Invest Dermatol). These enzymes function by cleaving extracellular adhesive proteins, such as corneodesmosin, desmoglein 1, and desmocollin 1, which maintain the structural integrity of the outermost epidermal layer (Hovnanian, 2013, Nat Rev Rheumatol). Their activity is strictly regulated by the skin's acid mantle, exhibiting optimal proteolysis at neutral to alkaline pH while being significantly inhibited in the acidic environment (pH ~5.5) of healthy skin (Elias, 2005, J Invest Dermatol). Dysregulation of these enzymes, frequently caused by the deficiency of their endogenous inhibitor LEKTI or pathological shifts in skin pH, leads to premature desquamation and severe barrier defects seen in conditions like Netherton syndrome and atopic dermatitis (Brattsand et al., 2005, J Invest Dermatol). Therapeutic interventions aim to restore the protease-antiprotease balance using topical serine protease inhibitors or pH-modulating agents to preserve skin barrier function (Quoin Pharmaceuticals, 2023).

Other names

Stratum corneum tryptic enzymeStratum corneum chymotryptic enzymeSCTESCCECorneocyte-desmosome degrading enzymespH-dependent desquamatory enzymes

Direct competitive inhibition of serine protease activity to prevent excessive degradation of corneodesmosomes; acidification of the stratum corneum to suppress pH-dependent enzyme activity.