Kallikrein-related peptidase 5, 7, and 14 (KLK5, KLK7, KLK14)

Kallikrein-related peptidases 5, 7, and 14 (KLK5, KLK7, KLK14) are serine proteases highly expressed in the human epidermis as part of a larger family of 15 homologous enzymes clustered on chromosome 19. They are synthesized and secreted as inactive zymogens, which are rapidly activated by proteolytic cleavage in a tightly regulated cascade: KLK5 can autoactivate and subsequently activate KLK7 and KLK14, while KLK14 in turn amplifies the cascade by re-activating additional KLK5. Their main physiological function is in corneocyte desquamation—the breakdown of corneodesmosome proteins (including desmocollin and corneodesmosin) that permit shedding of the stratum corneum and the maintenance of an effective skin barrier[3][5][6][8]. Aberrant activity leads to diseases such as ichthyosis, atopic dermatitis, Netherton syndrome, and several cancers[2][4]. Regulation involves local inhibitors (e.g. LEKTI, serpins), pH, and metal ions[1][3][5][6][8]. KLKs have also been implicated in inflammation and cell signaling, and are being investigated as potential therapeutic targets and disease biomarkers[2][4][6].

Other names

KLK5: Stratum corneum tryptic enzymeKLK7: Stratum corneum chymotryptic enzyme (SCCE)KLK14: KLK-L6General: Tissue kallikreinsSerine proteaseHuman tissue kallikrein

Direct enzymatic inhibition (competitive/irreversible binding to catalytic triad); Suppression of gene expression (e.g., ivermectin for KLK5)[8]; Interference with zymogen activation/activation cascade; Protease inhibitor (serpins, LEKTI)–mediated sequestration