LEKTI

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a is_associated_with::protein that in humans is encoded by the SPINK5 is_associated_with::gene.

Structure and function
LEKTI is a large multidomain is_associated_with::serine protease inhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease furin. Only two of these domains (2 and 15) contain 6 evenly spaced is_associated_with::cysteines responsible for 3 intramolecular is_associated_with::disulfide bonds characteristic of Kazal-type related inhibitors. The remaining domains contain 4 cysteines. These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended is_associated_with::beta-sheet. All domains (excepting 1, 2 and 15) contain an is_associated_with::arginine at P1, indicating trypsin-like proteases are the likely targets.

In the epidermis, LEKTI is implicated in the regulation of is_associated_with::desquamation via its ability to selectively inhibit is_associated_with::KLK5, is_associated_with::KLK7 and is_associated_with::KLK14. Recombinant full length LEKTI inhibits the exogenous serine proteases is_associated_with::trypsin, is_associated_with::plasmin, subtilisin A, is_associated_with::cathepsin G and human neutrophil is_associated_with::elastase.

LEKTI may play a role in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia.

Gene
SPINK5 is a member of a gene family cluster located on chromosome 5q33.1, which encode inhibitors of serine proteases. This includes other epidermal proteins is_associated_with::SPINK6 and is_associated_with::LEKTI-2 (SPINK9). The SPINK5 gene is 61 kb in length and contains 33 exons. Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.

Clinical significance
Mutations in the SPINK5 gene may result in is_associated_with::Netherton syndrome, a disorder characterized by is_associated_with::ichthyosis, defective cornification, and is_associated_with::atopy.