Collagen XVIIα1 in skin and hair aging: Mechanisms, stem cell niche regulation, and translational strategies

Collagen XVIIα1, encoded by COL17A1 and historically known as BP180/BPAG2, is a type II transmembrane collagen enriched in hemidesmosomes of basal keratinocytes. Through interactions with integrin α6β4, laminin-332 and other dermal-epidermal junction (DEJ) components, collagen XVIIα1 links the keratin cytoskeleton to the basement membrane. Recent studies indicate that this junctional anchorage supports epidermal homeostasis by preserving stem cell adhesion, polarity and regenerative capacity. During aging, collagen XVIIα1 levels decline and proteolytic processing increases, including ADAM9/ADAM10-dependent ectodomain shedding and cleavage by inflammatory proteases. These changes weaken DEJ integrity and are associated with photoaging and impaired repair. In hair follicles, collagen XVIIα1 is also required for hair follicle stem cell (HFSC) maintenance, and its reduction is linked to HFSC exhaustion, hair aging phenotypes and altered niche signals that may influence melanocyte stem cell-dependent pigmentation. This review summarizes translational approaches targeting collagen XVIIα1 and proposes practical in vivo readouts for target engagement. Key gaps include mechanism attribution, durable functional restoration at the DEJ, persistence within the epidermal-follicular niche and a shortage of rigorous human studies.