Skin Barrier Insights: From Bricks and Mortar to Molecules and Microbes.

Recent advances in genomics, spectroscopy, and immunology have increased our understanding of the skin barrier. A new model of barrier lipid organization has emerged owing to the application of advanced modeling and microscopy techniques. The contribution of filaggrin gene mutations to atopic dermatitis has increased our appreciation of the role barrier perturbations play in inflammatory dermatoses.

Regulatory role for the profilaggrin N-terminal domain in epidermal homeostasis.

It is well known that profilaggrin, after its release from keratohyalin granules through dephosphorylation, becomes enzymatically processed into individual filaggrin monomers. The roles for filaggrin monomers in aggregating keratin filaments, as a component of the cornified cell envelope, and as a source of natural moisturizing factor are well established. A specific N-terminal fragment, called the PF-AB domain, becomes proteolytically released as well, but much less is known about its functional role in epidermal development.