The Lysosomal Protease Cathepsin L Is an Important Regulator of Keratinocyte and Melanocyte Differentiation During Hair Follicle Morphogenesis and Cycling

The study demonstrated that cathepsin L (CTSL) was crucial for proper hair follicle development and cycling in ctsl(-/-) mice. Deficiencies in CTSL led to abnormal keratinocyte and melanocyte differentiation, resulting in disrupted hair shaft outgrowth, increased proliferation and apoptosis, and vacuolation of melanocytes. Hair cycling was delayed, with a shortened resting phase and premature growth phase entry. Additionally, there were issues with hair shaft exit due to incomplete desquamation of the inner root sheath, causing hair canal dilation and abnormal sebaceous gland product routing. These findings highlighted the significant roles of cathepsin proteases in skin, hair, and pigment biology.