Stratum corneum and keratinocyte layer of the skin (SC)

The stratum corneum and keratinocyte layers constitute the epidermis, the outermost tissue of the skin that serves as a critical biosensor and protective barrier (StatPearls, 2023). The stratum corneum, the most superficial layer, is composed of flattened, dead keratinocytes (corneocytes) surrounded by a complex lipid matrix of ceramides, cholesterol, and fatty acids, which prevents excessive transepidermal water loss and blocks the entry of environmental toxins (NIH, 2022). Beneath this, the living keratinocyte layers (granulosum, spinosum, and basale) are responsible for the continuous regeneration of the skin through a highly regulated process of proliferation and terminal differentiation (PubMed, 2021). Dysregulation of these layers is a hallmark of various dermatological conditions; for instance, psoriasis involves keratinocyte hyperproliferation, while atopic dermatitis is characterized by a defective stratum corneum barrier often linked to filaggrin deficiency (Mayo Clinic, 2023). Although not a single molecular target like a receptor or enzyme, this anatomical region is the primary site for topical drug delivery and is modulated by therapies ranging from keratolytics and retinoids to anti-inflammatory corticosteroids (PubChem, 2024). Understanding the physical and biochemical properties of these layers is essential for developing effective transdermal treatments and managing skin barrier diseases.

Other names

EpidermisSkin barrierHorny layerStratum corneumKeratinocyte layer

Topical agents interact with these layers through various mechanisms: keratolytics like salicylic acid dissolve the intercellular cement in the stratum corneum to promote desquamation; retinoids like tretinoin bind to nuclear receptors in keratinocytes to normalize differentiation and proliferation; and emollients/humectants like ceramides and urea restore the lipid barrier and increase water-binding capacity (StatPearls, 2023; PubChem, 2024).