KRT2

KRT2 Full Name

keratin 2

KRT2 Introduction

KRT2, also known as keratin 2 or cytokeratin-2e, encodes a type II intermediate filament protein that is a core structural component of differentiated keratinocytes in stratified squamous epithelia, particularly the upper spinous and granular layers of the epidermis. Like other members of the keratin family, KRT2 partners with type I keratins to form heterodimeric filaments that contribute to the cytoskeletal network, support mechanical resilience, and participate in terminal cornification as keratinocytes transition to corneocytes. Its expression pattern reflects roles in both normal epidermal barrier formation and in the phenotypic properties of other keratinizing epithelia, and it is regulated alongside other keratins during keratinocyte activation, proliferation and differentiation.

Figure 1.Impact of KRT2 on epidermal integrity. The left panel shows normal KRT2-Type I filament networks providing mechanical resilience. The right panel depicts KRT2 loss, leading to filament disorder, hyperkeratosis, and impaired barrier function.

Functionally, the KRT2 protein is not only a structural constituent of the epidermis but also contributes to maintaining skin integrity and barrier function. Experimental models have shown that loss of KRT2 expression can lead to disordered intermediate filament organization, hyperkeratosis, enhanced keratinocyte proliferation, and increased skin water loss, highlighting its importance in maintaining corneocyte stability and normal skin architecture. These features reflect a role in the positive regulation of epidermis development, keratinocyte migration and keratinization, and in reinforcing the cytoskeletal network necessary for withstanding mechanical stress.

Clinically, mutations in KRT2 are most notably associated with superficial epidermolytic ichthyosis (formerly ichthyosis bullosa of Siemens), an autosomal dominant keratinopathic ichthyosis characterized by mild to moderate hyperkeratosis, superficial blistering, and skin fragility, particularly in regions subject to friction. Specific pathogenic variants, including recurrent mutations affecting helix termination motifs, disrupt filament assembly and lead to the characteristic epidermal phenotype observed in patients, with some mutations documented in ClinVar. Beyond this primary association, differential regulation of KRT2 expression has also been observed in conditions such as psoriasis and other disorders of keratinization, underscoring its broader relevance in cutaneous biology and pathology.

Alternate Names for KRT2

KRT2; keratin 2; K2e; KRTE; CK-2e; KRT2A; KRT2E; keratin, type II cytoskeletal 2 epidermal; keratin-2e; cytokeratin-2e; keratin-2 epidermis; type-II keratin Kb2; epithelial keratin-2e;

• 1. Mohamad J, et al.; Epidermolytic epidermal nevus caused by a somatic mutation in KRT2. Pediatr Dermatol. 2021, 38(2):538-540.