Keratin, type I cytoskeletal 9 (KRT9) (KRT9)

Keratin, type I cytoskeletal 9 (KRT9) is a structural protein specifically expressed in the suprabasal layers of the palmoplantar epidermis, which includes the skin of the palms and soles (UniProt P35527). Its primary biological function is to provide mechanical strength and structural integrity to these specialized skin areas, enabling them to withstand high levels of friction and pressure (PubMed: 23962810). Mutations in the KRT9 gene are the primary cause of Epidermolytic Palmoplantar Keratoderma (EPPK), a rare autosomal dominant disorder characterized by severe hyperkeratosis, blistering, and pain (GeneCards). Because the disease typically results from dominant-negative mutations, KRT9 has become a significant therapeutic target for gene-silencing technologies such as siRNA and gene-editing tools like CRISPR/Cas9 (PubMed: 22584502, 31521640). Experimental therapies aim to specifically inhibit the mutant allele to restore normal keratin network formation and skin function. Beyond its role in skin disease, KRT9 has recently been identified as a potential plasma biomarker for Alzheimer's disease, suggesting broader physiological implications (ResearchGate: 10). Therapeutic development remains focused on overcoming delivery challenges to the thick palmoplantar skin and ensuring allele specificity to avoid compromising the structural role of wild-type Keratin 9.

Other names

Keratin-9Cytokeratin-9CK-9K9EPPKEPPK1Type I cytoskeletal 9

Allele-specific gene silencing via RNA interference (RNAi) and gene editing via CRISPR/Cas9