corneodesmosomes

Corneodesmosomes are specialized cell–cell adhesion structures located in the stratum corneum of the epidermis. They are modified desmosomes that persist between adjacent corneocytes, the enucleated cells of the outermost skin layer. Corneodesmosomes maintain cohesion during terminal differentiation and are dismantled in a controlled manner to permit desquamation, the shedding of corneocytes, which is essential for barrier turnover and skin homeostasis.

Structurally, corneodesmosomes incorporate classical desmosomal cadherins such as desmoglein 1 and desmocollin 1, along with plakophilin 1 and other plaque proteins. A key corneodesmosomal component is corneodesmosin, a protein enriched in the stratum corneum that reinforces intercellular adhesion in this dense, anucleate layer. The overall composition supports robust linkage to keratin intermediate filaments within corneocytes, facilitating cohesive cell–cell contact in the outer skin.

Regulation and turnover are central to corneodesmosome function. Proteolytic enzymes, notably kallikreins KLK5 and KLK7, cleave corneodesmosomal proteins to promote desquamation. This proteolysis is tightly controlled by inhibitors such as LEKTI (encoded by SPINK5); loss or dysfunction of inhibition leads to excessive corneodesmosome degradation and barrier impairment, as seen in Netherton syndrome. Environmental factors, pH, and inflammatory signals can also influence corneodesmosome disassembly.

Clinical relevance includes alterations in corneodesmosome composition or turnover in various skin disorders, such as ichthyoses, atopic dermatitis, and psoriasis, where impaired adhesion or accelerated shedding contributes to abnormal scaling and barrier dysfunction. Ongoing research aims to further clarify corneodesmosome assembly and disassembly mechanisms as potential therapeutic targets to restore barrier integrity.