BACKGROUND: Several skin diseases and atopic disorders including Netherton 
syndrome and atopic dermatitis have been associated with mutations and 
deviations of expression of SPINK5, the gene encoding the human 15-domain serine 
proteinase inhibitor LEKTI. The biochemical mechanisms underlying this 
phenomenon have not yet been fully clarified.
OBJECTIVES: To identify target proteinases of LEKTI important for processes of 
desquamation and inflammation of the skin which will enable the development of 
specific drugs.
METHODS: The inhibitory activities of LEKTI domains 6 and 15 were tested on a 
number of commercially available serine proteinases and also on the purified 
kallikreins hK5 and hK7. In addition, recombinant hK5 was used.
RESULTS: LEKTI domain 6 is a potent inhibitor of hK5 and hK7, whereas LEKTI 
domain 15 exhibits inhibitory activity on plasmin. hK5 and hK7 in particular are 
relevant to skin disorders.
CONCLUSIONS: The inhibition of hK5 and hK7 by LEKTI domain 6 indicates an 
important regulatory role of LEKTI in processes of skin desquamation and 
inflammation, which may explain the severe pathological symptoms associated with 
abnormalities of SPINK5 and/or its expression. Thus, LEKTI represents a 
potential drug for the treatment of these disorders.