Keratinocyte differentiation and stratum corneum cohesion pathways

Keratinocyte differentiation and stratum corneum cohesion pathways encompass the coordinated molecular events required for the formation and maintenance of the epidermal barrier. Keratinocytes undergo a complex maturation process from the basal layer to the stratum corneum, involving the sequential expression of structural proteins like filaggrin and involucrin, which are cross-linked by transglutaminases to form the cornified envelope (PMID: 28110940). Cohesion within the outermost layer is maintained by corneodesmosomes, specialized cell-cell junctions that must be precisely degraded by kallikrein-related peptidases to facilitate healthy desquamation (PMID: 21691577). Defects in these pathways, such as filaggrin mutations or excessive protease activity, lead to skin barrier dysfunction seen in atopic dermatitis, psoriasis, and various forms of ichthyosis (NIH: NBK470464). Therapeutic strategies often focus on restoring barrier integrity, either through topical retinoids and vitamin D analogs that normalize differentiation or through systemic biologics like dupilumab that indirectly restore barrier protein expression by inhibiting Th2 cytokine signaling (PMID: 30124578). Because this entry describes a broad biological process involving multiple proteins and enzymes rather than a single molecular entity, it is classified as a pathway rather than a discrete therapeutic target.

Other names

Epidermal differentiation complex pathwaysSkin barrier functionDesquamation processCorneocyte maturationKeratinization pathway

Modulation of keratinocyte gene expression and enzymatic activity to restore structural integrity and regulate the desquamation process.