COL17A1 encodes type XVII collagen (COL17A1/BP180), a transmembrane collagen that serves as a critical structural component of hemidesmosomes and basement membrane zones 1. The protein functions as an anchoring filament component involved in dermal-epidermal cohesion and is essential for maintaining epithelial stem cell populations across multiple tissues 12. COL17A1 plays a pivotal role in stem cell maintenance through direct regulation of cell motility and collective cell migration by coordinating actin and keratin filament networks 2. The protein undergoes age-related proteolysis, which triggers stem cell aging and terminal differentiation, leading to tissue miniaturization in hair follicles 1. COL17A1 is also crucial for maintaining dormant cancer stem cells through strengthening cell-matrix interfaces, with its disruption leading to chemotherapy resistance 3. Disease relevance includes junctional epidermolysis bullosa type 4 caused by COL17A1 mutations 4 and epithelial recurrent erosion dystrophy 5. The protein is expressed in gastrointestinal epithelia as a marker of quiescent stem/progenitor cells 6 and shows altered expression in melanoma metastasis 7. COL17A1's dual role in tissue homeostasis and disease pathogenesis makes it a potential therapeutic target for age-related disorders and cancer treatment.