KLK5

KLK5, kallikrein-related peptidase 5, previously named stratum corneum tryptic enzyme, is a secreted serine protease predominantly expressed in epidermal keratinocytes. It facilitates corneocyte shedding, activates PAR2 and processes cathelicidin precursor into functional LL-37 to maintain epidermal barrier and local cutaneous immunity.

Unrestrained KLK5 activity due to LEKTI deficiency triggers severe skin inflammation and barrier breakdown, serving as a primary driver of Netherton syndrome. Excessive KLK5 also promotes pathological inflammation in rosacea. Selective small-molecule inhibitors and neutralizing antibodies targeting KLK5 are under preclinical assessment for inflammatory and hereditary skin disorders.