Stratum corneum skin proteins (SC proteins)

The stratum corneum (SC) is the outermost layer of the epidermis, functioning as the body's primary physical and chemical barrier. It is composed of enucleated, protein-rich corneocytes embedded in a specialized lipid matrix, often described as a "brick-and-mortar" structure [3, 10]. Key proteins include keratins, which provide structural integrity; filaggrin, which aggregates keratins and is later catabolized into Natural Moisturizing Factors (NMF) to maintain hydration; and corneodesmosomal proteins like corneodesmosin, which mediate cell-cell adhesion [1, 11, 22]. These proteins are essential for maintaining the skin's permeability barrier, protecting against mechanical and microbial insults, and regulating the orderly shedding of skin cells (desquamation) through the action of proteolytic enzymes like kallikreins [1, 16]. Dysfunction or deficiency in stratum corneum proteins is a hallmark of several dermatological diseases, most notably atopic dermatitis (linked to filaggrin mutations), psoriasis (characterized by hyperkeratosis and parakeratosis), and various forms of ichthyosis [3, 20, 22]. Therapeutic strategies often target these proteins to restore barrier function or manage hyperkeratotic conditions. For example, keratolytics such as salicylic acid and urea disrupt protein-protein interactions to facilitate exfoliation, while topical retinoids modulate the degradation of corneodesmosomes to accelerate skin turnover [11, 16, 18]. Furthermore, the stratum corneum acts as a critical pharmacological reservoir for topically applied drugs, significantly influencing their penetration kinetics and therapeutic efficacy [9, 21].

Other names

Corneocyte proteinsEpidermal barrier proteinsCornified envelope proteinsKeratinocyte-derived proteins

Drugs targeting these proteins typically act via keratolytic activity (breaking down keratin and corneodesmosomes to promote shedding), humectant effects (binding water to proteins like filaggrin-derived NMF), or by modulating the differentiation and desquamation cycle of corneocytes. Some agents also utilize the stratum corneum as a reservoir for sustained drug release into deeper skin layers.