KRT1 (keratin 1) encodes a major structural intermediate filament protein that plays critical roles in epidermal integrity and cellular signaling. As a key component of the cytoskeleton, KRT1 forms heterodimers with KRT10 in suprabasal differentiated keratinocytes of normal skin epidermis 1. The protein serves as a differentiation marker, with downregulated expression indicating loss of normal epidermal differentiation 2. Beyond its structural role, KRT1 functions in cellular signaling pathways, including interaction with phosphoglycerate kinase 1 (PGK1) to stabilize cytoskeletal integrity 3 and binding to carcinoembryonic antigen (CEA) to activate PI3K/AKT signaling pathways 4. KRT1 mutations cause various inherited keratodermas and ichthyoses, including palmoplantar keratoderma and epidermolytic hyperkeratosis 5. Interestingly, while human KRT1 missense variants typically cause epidermolytic hyperkeratosis, a deletion variant in dogs resulted in non-epidermolytic ichthyosis, suggesting species-specific functional differences 6. The protein also serves as a skin barrier marker in wound healing studies, with increased expression indicating restored epidermal barrier function 7. These findings establish KRT1 as both a crucial structural component and signaling mediator in epidermal homeostasis.