SPINK5 (Serine Peptidase Inhibitor Kazal-Type 5) encodes LEKTI (Lympho-Epithelial Kazal-Type-Related Inhibitor), a multidomain serine protease inhibitor critical for skin barrier integrity and immune regulation. Expressed in stratified epithelia (e.g., skin, thymus), LEKTI modulates proteolytic cascades by inhibiting kallikreins and other proteases that regulate desquamation, inflammation, and antimicrobial defense. Mutations in SPINK5 cause Netherton syndrome, a severe autosomal recessive disorder characterized by congenital ichthyosiform erythroderma, hair shaft defects, and atopic manifestations due to uncontrolled protease activity and epidermal disruption.
LEKTI antibodies are tools used in research and diagnostics to detect protein expression, localization, or deficiency in tissues. In Netherton syndrome, reduced/absent LEKTI detected via immunohistochemistry aids diagnosis. Research applications include studying LEKTI's role in skin homeostasis, inflammatory pathways (e.g., PAR-2 signaling), and therapeutic strategies (e.g., protease inhibitors or gene therapy). Commercial antibodies target specific LEKTI domains (e.g., D9. D15) to assess functional fragments. Challenges include cross-reactivity due to LEKTI's complex 15-domain structure and post-translational processing. Recent studies also explore LEKTI's potential as a biomarker in atopic dermatitis and cancer.