The primary functions of the epidermis include water retention, thermal and pH homeostasis, and protection against entry of pathogenic microbes or toxic substances into the body. 1, 2 Appropriate epidermal barrier formation relies on progressive differentiation of keratinocytes from the proliferating cells within the basal cell layer to the terminally differentiated cornified layer or stratum corneum. 2 The stratum corneum is composed of keratin macrofibrils and cross-linked cornified envelopes encased in lipid bilayers. Filaggrin (FLG) and lipids produced by epidermal granular cells control the assembly of a lipid-keratin matrix in forming this semipermeable barrier. Defects in the integrity of the epidermal barrier can result in a variety of inflammatory skin disorders, including atopic dermatitis (AD) and ichthyosis.

Ichthyosis is characterized by the presence of excessive amounts of dry, scaly, and thick skin surface. The cause of the ichthyosis is attributed to the complex interplay between keratinocyte differentiation and metabolic dysregulation. Genetic and clinical evidence indicates that defective expression and function of genes involved in FLG processing and lipid synthesis impair epidermal barrier acquisition and drive the onset of ichthyosis, 1 resulting in water loss, entry of infectious microbes, and infiltration of inflammatory lymphocytes. From a developmental perspective, it has been proposed that balancing keratinocyte