Lympho-Epithelial Kazal-Type-related Inhibitor (LEKTI) has been demonstrated to 
be an inhibitor of various kallikreins and is thought to play a role in the 
regulation of skin desquamation. In order to identify and investigate the 
potential of LEKTI to interact with other proteins, a method was developed using 
immobilised proteins onto arrays and nanoUPLC/MALDI-TOF MS. Using various 
domains of LEKTI, we demonstrated that these domains bound a number of 
kallikreins (5, 13 and 14) to varied extents on the array surface. Inhibitory 
assays confirmed that binding on the protein array surface corresponded directly 
to levels of inhibition. The method was then tested using skin epidermal 
extracts. All forms of rLEKTI with the exception of rLEKTI 12-15, demonstrated 
the binding of several potential candidate proteins. Surprisingly, the major 
binding partners of LEKTI were found to be the antimicrobial peptide dermcidin 
and the serine protease cathepsin G and no kallikreins. Using confocal 
microscopy and Netherton syndrome skin sections, we confirmed the 
co-localisation of LEKTI with dermcidin and demonstrated altered trafficking of 
dermcidin in these patients. This potential new role for LEKTI as a 
multifunctional protein in the protection and transport of proteins in the 
epidermis and its role in disease are discussed.