KRT25 (keratin 25) is a type I keratin essential for proper assembly of type I-II keratin heterodimers and formation of keratin intermediate filaments within the inner root sheath (IRS) of hair follicles 1. It plays a critical role in cytoskeleton organization and epithelial cell differentiation, contributing to hair follicle morphogenesis and maintenance of hair texture 1. Functionally, KRT25 participates in protein heterodimerization and intermediate filament organization within the cytoskeleton 2. Homozygous missense variants in KRT25 cause woolly hair autosomal recessive 3 (ARWH3), characterized by tightly curled sparse hair; mutations disrupt the α-helical rod domain, impairing keratin heterodimerization within the IRS and hair medulla 13. Beyond hair disorders, KRT25 dysfunction associates with other conditions: downregulation occurs in vesicular hand eczema alongside aberrant epidermal differentiation 4, reduced expression characterizes alopecia areata lesions correlating with loss of follicular structural integrity 5, and variants associate with asthma treatment response and periodontitis 67. KRT25 expression in basal cell carcinoma correlates with IRS differentiation 8. These findings establish KRT25 as a critical structural protein for hair follicle development with broader implications for epithelial and immunological disorders.