SERPINB7 is a serine protease inhibitor primarily functioning to maintain epidermal barrier integrity through multiple mechanisms. It acts as an inhibitor of the cysteine protease legumain 1, directly binding and suppressing legumain activity both in vitro and in vivo. SERPINB7 regulates protein O-GalNAc glycosylation, which is essential for proper tight junction formation, calcium signaling, and cell adhesion in keratinocytes 2. Loss-of-function mutations in SERPINB7 cause Nagashima-type palmoplantar keratoderma, an autosomal recessive genodermatosis characterized by disrupted skin barrier function, weakened cytoskeletal proteins, and impaired epidermal differentiation 1. SERPINB7 deficiency also exacerbates psoriasis by impairing keratinocyte differentiation and reducing intracellular calcium flux 3. Beyond skin disease, SERPINB7 has been identified as a food allergy susceptibility gene involved in epithelial barrier function 4. In infection contexts, SERPINB7 is upregulated during Mycobacterium tuberculosis antigen stimulation, suggesting involvement in immune responses 5. Additionally, SERPINB7 expression levels may serve as a biomarker for predicting responses to intravenous vitamin C treatment in non-small-cell lung cancer 6.