SPINK5

The lymphoepithelial Kazal-type-related inhibitor (LEKTI) encoded by the serine protease inhibitor Kazal type 5 (SPINK5) is distributed in stratified epithelial tissue. The epidermis is mainly in the granular layer. LEKTI has 15 Kazal-type serine peptidase inhibitor regions (D1-D15). The full-length recombinant protein can inhibit trypsin, plasmin, substilisin A, cathepsin G and elastase. The D5 and D6 regions only inhibit trypsin; the part containing D6-D9 takes histones to inhibit trypsin and substilisin A. Without inhibiting plasmin, cathepsin G and elastase, LEKTI may play a role in multiple biological pathways in homeostasis, inflammation and infection.
LEKTI participates in the maintenance and balance of FLG metabolism and skin barrier function by inhibiting the activity of various proteases such as Matriptase, CAP1, caspasel4, SCCE and SCTE during epidermal differentiation. LEKTI inhibits excessive degradation of FLG mainly by inhibiting Matriptase, CAPI, and caspase14; it can also prevent excessive desquamation caused by premature keratinocyte maturation by inhibiting SCCE SCTE activity. Therefore, LEKTI is the key to maintain the epidermal barrier and skin appearance. Protease. Low expression of LEKTI can increase the activity of SC-CE and SCTE, aggravate the inflammatory reaction and excessive desquamation. The typical case is the defect of the LEKTI protein-coding gene SPINKS caused by AD-like skin lesions in the Netherton syndrome of gene-deficient skin disease.