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Target intelligence / Profile preview
Serine protease inhibitor Kazal-type 5 (SPINK5)
- Target
- SPINK5
- Molecular classification
- Enzyme inhibitor (serine protease inhibitor), Kazal-type serine protease inhibitor family
01
Overview
Serine protease inhibitor Kazal-type 5 (SPINK5), also known as lympho-epithelial Kazal-type-related inhibitor (LEKTI), is a large multidomain serine protease inhibitor expressed primarily in stratified epithelial tissues, notably in the skin. It contains 15 protease inhibitor domains and is essential for regulating skin barrier function by inhibiting epidermal serine proteases such as KLK5, KLK7, and KLK14. LEKTI fragments modulate desquamation (the shedding of skin cells), and protect mucous epithelia against inflammation and microbial invasion. Mutations in the SPINK5 gene result in Netherton syndrome, a rare genetic disorder marked by congenital ichthyosis, immune dysregulation, and susceptibility to infections[1][2][4][6].
- Other names
- Lympho-epithelial Kazal-type-related inhibitor (LEKTI)SPINK5LEKT1
02
Mechanism of action
Inhibition of serine proteases including KLK5, KLK7, KLK14, trypsin, plasmin, subtilisin A, cathepsin G, and human neutrophil elastase[1]
03
Biological functions
Regulation of skin desquamationInhibition of epidermal serine proteasesMaintenance of epithelial barrier functionAnti-inflammatory protectionAntimicrobial protection
04
Disease associations
Netherton syndrome (caused by SPINK5 mutations; presents with ichthyosis, immune dysfunction)Possible involvement in other skin barrier disorders
05
Safety considerations
Loss-of-function mutations cause severe skin barrier dysfunction and immune dysregulation[1]
06
Biomarkers
SPINK5/LEKTI deficiency is a biomarker for Netherton syndrome
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