Netherton Syndrome

Netherton syndrome is caused by loss-of-function mutations in SPINK5, which encodes the protease inhibitor LEKTI. Unchecked serine protease activity thins the stratum corneum and reduces ceramides, producing severe, persistent atopic dermatitis and allergies. It offers a clue that excess protease activity can provoke AD (Elias & Wakefield 2011).

Connections

• Skin Barrier Dysfunction — model of protease-driven barrier failure, source: Elias & Wakefield 2011
• Differential Diagnosis of Toddler Eczema — erythroderma + hair-shaft defect + failure to thrive red flag, source: Türe Avcı 2026