Molecular and Biochemical Properties of Lympho-Epithelial Kazal-Type-Inhibitor (LEKTI)

Abstract

Here, we review the literature on the molecular and biochemical properties of Lympho-Epithelial Kazal-Type-Inhibitor (LEKTI). Serine Protease Inhibitor Kazal- type 5 (SPINK5) gene encodes three different LEKTI isoforms. These isoforms are organized into a typical 15, longer than 15 and shorter than 15 inhibitory domains consisting of 1064, 1094 and 916 residues respectively. LEKTI isoforms synthesized as pro-LEKTI proteins are processed intracellular and secreted as bioactive LEKTI fragments into blood. LEKTI potently inhibits activity of plasmin, subtilisin A, cathepsin G, elastase, trypsin, kallikrein (KLK) 5, KLK6, KLK7, KLK13, and KLK14 to varied extents. Mutations in SPINK5 gene resulting in decreased LEKTI function and increased KLK activity causes Netherton syndrome (NS). Low SPINK5 expression/LEKTI function is also associated with Head and Neck Squamous Cell carcinoma (HNSCC), chronic rhinosinusitis and asthma. Thus restoring SPINK5 expression/LEKTI function in NS, HNSCC and asthma holds therapeutic promise.