Basement membrane zone proteins in wound healing: Insights from epidermolysis bullosa models

Abstract The epidermal basement membrane zone (eBMZ) plays a central role in skin integrity and regeneration by anchoring keratinocytes to the underlying dermis and supporting epidermal stem cell maintenance. Inherited defects in eBMZ proteins cause epidermolysis bullosa (EB), a group of mechanobullous disorders characterized by skin fragility and chronic wounds. While the importance of eBMZ proteins in maintaining epidermal architecture is well recognized, their dynamic involvement in wound healing remains incompletely understood. This review highlights recent insights into the role of key eBMZ proteins in cutaneous wound repair. We summarize evidence from EB mouse models, which commonly exhibit delayed wound healing due to distinct molecular defects. Emerging findings suggest that eBMZ proteins influence keratinocyte migration, basement membrane remodeling, and inflammatory responses, and that some may serve as modulators of epidermal stem cell behavior. Elucidating the mechanistic functions of eBMZ components during tissue repair may foster the development of targeted therapies for wound healing in EB and other chronic skin disorders.