Kallikrein-related peptidase 5 (KLK5) (KLK5)

Kallikrein-related peptidase 5 (KLK5) is a secreted serine protease primarily expressed in the epidermis, where it serves as a master regulator of skin homeostasis and desquamation [5, 6]. It functions by cleaving corneodesmosomal proteins, such as desmoglein 1 and corneodesmosin, and by initiating a proteolytic cascade that activates other kallikreins, including KLK7 and KLK14 [6, 8]. Under normal physiological conditions, KLK5 activity is strictly regulated by the endogenous inhibitor LEKTI; however, deficiency of LEKTI—as seen in Netherton syndrome—leads to uncontrolled KLK5 activity, resulting in severe skin barrier disruption, chronic inflammation, and allergic manifestations [6, 9]. Beyond its role in rare genetic skin disorders, KLK5 is implicated in the pathogenesis of common inflammatory conditions like atopic dermatitis and rosacea, as well as various malignancies where it often serves as a prognostic biomarker [7, 16, 20]. In cancer, KLK5 can promote tumor cell invasion and metastasis by remodeling the extracellular matrix [16, 20]. Therapeutic strategies targeting KLK5 focus on the development of selective inhibitors, including small molecules and monoclonal antibodies, to restore the proteolytic balance in the skin and alleviate inflammatory symptoms [7, 15]. Several candidates, such as BCX17725 and GSK951, have entered clinical or advanced preclinical development for the treatment of Netherton syndrome and related dermatoses [11, 15].

Other names

Kallikrein-5Stratum corneum tryptic enzymeSCTEKLK-L2KLKL2Human kallikrein 5hK5

Serine protease inhibition