Col17a1, which encodes type XVII collagen (also known as BP180), is a critical molecule for the maintenance of hair follicle stem cells (HFSCs) and is involved in the hemidesmosome component at the epidermal-dermal junction [1,3]. It plays a key role in skin-related biological processes, and its proteolysis is associated with several pathways related to skin aging and regeneration [1,2]. Genetic models, especially knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying its function.

In KO mouse models, Col17a1 deficiency recapitulates the hair follicle aging process, characterized by the stepwise miniaturization of hair follicles and eventual hair loss due to the transepidermal elimination of HFSCs [1]. Forced maintenance of COL17A1 in HFSCs can prevent this aging process, demonstrating its central role in the stem-cell-centric aging program of the epithelial mini-organ [1]. Also, in skin regeneration, EGFR-mediated signaling is linked to COL17A1 proteolysis, affecting keratinocyte stem cell dynamics [2]. Stem cell competition in the skin is orchestrated by the differential expression of COL17A1, with clones expressing high levels outcompeting those with low levels, and its loss contributing to skin aging [3].

In conclusion, Col17a1 is essential for maintaining the homeostasis of skin-related stem cells, especially in hair follicles and epidermis. Mouse KO/CKO models have significantly contributed to understanding its role in skin aging and regeneration, highlighting its potential as a target for anti-aging therapeutic intervention [1,2,3].