KRT9 (keratin 9) is a type I intermediate filament protein with specialized functions in palmoplantar epidermis. It plays a critical structural role in keratin filament assembly and is essential for proper epidermal differentiation in palmar and plantar skin 1. KRT9 forms heterodimeric complexes with type II keratins, particularly KRT6C, to organize cytoskeleton and regulate keratinization processes 2. Beyond structural functions, KRT9 participates in innate immunity: it directly interacts with guanylate binding protein 5 (GBP5) to facilitate transport of respiratory syncytial virus small hydrophobic protein, thereby suppressing viral replication 3. Mutations in KRT9 cause epidermolytic palmoplantar keratoderma (palmoplantar keratoderma, epidermolytic, 1), characterized by excessive keratin accumulation on palms and soles 45. Disease-causing variants include missense mutations affecting the conserved helix 1A region, disrupting normal intermediate filament function 5. KRT9 downregulation has also been observed in gastric cancer patients, suggesting potential roles in mucosal defense 6. Clinical significance includes genetic testing enabling accurate diagnosis and preimplantation genetic testing to prevent disease transmission 5.