KRT14 (keratin 14) is a structural intermediate filament protein predominantly expressed in basal layer keratinocytes and other stratified epithelia. 1 Its primary function involves assembling with KRT5 to form the basal cytoskeletal network that provides mechanical resilience to epithelial tissues. 2 KRT14-KRT5 heterodimers are restricted to proliferative basal cells, while their expression is downregulated during keratinocyte differentiation when KRT10-KRT1 becomes predominant. 2 KRT14 contributes to both normal epithelial homeostasis and pathological processes. In wound healing and diabetic ulcers, KRT14+ keratinocytes serve as markers of basal proliferative cells undergoing repair. 3 Beyond structural roles, KRT14 has emerged as a functional player in disease progression: elevated KRT14 expression driven by EZH2-H3K27me3 signaling promotes triple-negative breast cancer peritoneal metastasis through enhanced cell migration and invasion. 4 Additionally, keratinocyte-specific KRT14-driven expression systems reveal that KRT14+ cells regulate inflammatory responses, particularly through HMGB1-associated autophagy in psoriasis pathogenesis. 5 Mutations in KRT14 cause epidermolysis bullosa simplex (EBS), a blistering disorder affecting approximately 6-30 per million births, arising from impaired cytoskeletal integrity in basal keratinocytes. 6 KRT14 also marks specialized progenitor populations in bone regeneration and thymic tumors, suggesting broader developmental roles beyond traditional epithelial functions.