Gene SPINK5
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Also known as
LEKTI, Lympho-Epithelial Kazal-Type-Related Inhibitor, NS2, NETSOverview
SPINK5 (Serine Protease Inhibitor Kazal-Type 5) encodes LEKTI (Lympho-Epithelial Kazal-Type-Related Inhibitor), a large multidomain serine protease inhibitor that is crucial for maintaining skin barrier function. LEKTI is expressed predominantly in epithelial tissues, particularly in the uppermost layers of the epidermis, where it regulates the activity of multiple kallikrein-related peptidases (KLKs). These proteases are essential for proper desquamation, the controlled shedding of dead skin cells from the stratum corneum. By inhibiting premature or excessive protease activity, SPINK5 ensures proper skin barrier formation and integrity. The protein is processed into multiple functional inhibitory domains, each capable of targeting different proteases involved in skin homeostasis.Mutations in SPINK5 cause Netherton syndrome, a severe autosomal recessive disorder characterized by congenital ichthyosis, a distinctive hair shaft abnormality called trichorrhexis invaginata, and atopic manifestations including elevated IgE levels and increased susceptibility to allergies and infections. Loss of LEKTI function leads to excessive protease activity, resulting in abnormal desquamation, compromised skin barrier, and increased transepidermal water loss. Beyond Netherton syndrome, genetic variants in SPINK5 have been associated with increased susceptibility to atopic dermatitis and other inflammatory skin conditions. Understanding SPINK5 function has important implications for developing therapeutic strategies for various skin barrier disorders and may inform personalized skincare approaches.