KRT5

KRT5, or keratin 5, is a protein-coding gene that encodes a type II cytokeratin. In humans, the KRT5 protein pairs with keratin 14 (KRT14) to form the keratin intermediate filament network in basal keratinocytes of stratified epithelia, including the epidermis. This heterodimerization is essential for the assembly and stability of the keratin filament system.

Expression of KRT5 is highest in the basal layer of the epidermis and in other proliferative epithelia. The keratin 5/14 network provides mechanical resilience to cells, helping them withstand shear and stretch, and it integrates with desmosomes and other cytoskeletal elements to maintain tissue integrity.

Clinical significance: Pathogenic variants in KRT5 cause epidermolysis bullosa simplex (EBS), a hereditary skin fragility disorder characterized by blistering following minor trauma. Most KRT5-related EBS forms are inherited in an autosomal dominant pattern; the phenotype ranges from localized blistering to generalized skin involvement, depending on the mutation. Mutations disrupt filament assembly, leading to weakened keratinocytes and cytolysis under mechanical stress.

Genetics and history: The KRT5 gene is located on chromosome 12 in humans and is part of the keratin gene family. Genetic testing can identify pathogenic variants in KRT5 and support diagnosis and genetic counseling.