SERPINB8 is a serine protease inhibitor with critical roles in epithelial cell-cell adhesion and tissue homeostasis. Mechanistically, SERPINB8 functions as an intracellular inhibitor of furin, a prohormone convertase involved in inflammation and extracellular matrix remodeling 1. The protein localizes to the cytoplasm and extracellular matrix, where it regulates desmosomal adhesion integrity 2. Loss-of-function mutations in SERPINB8 cause peeling skin syndrome 5, characterized by exfoliative ichthyosis resulting from impaired mechanical stability of keratinocyte intercellular adhesions and keratinocyte disadhesion in lower epidermal layers 2. Beyond dermatologic disease, SERPINB8 variants have been identified as candidate genes in familial pulmonary fibrosis 3 and show associations with psoriasis in Chinese populations 4. In melanoma, SERPINB8 regulates ITGAX expression through physical binding to furin, modulating cell proliferation and invasion 5. SERPINB8 is also expressed in neuroendocrine tissues, particularly pancreatic beta cells, serving as a diagnostic immunohistochemical marker for pancreatic neuroendocrine tumors 6. During kidney regeneration, SERPINB8 redistribution suggests involvement in tissue repair processes 7. Clinically, SERPINB8 dysfunction impacts skin barrier integrity, tissue remodeling, and potentially oncogenic processes.