The Acid Mantle Reimagined: Unveiling the Role of Stepwise pH Zonation in the Stratum Corneum

Abstract

The stratum corneum (SC), the outermost layer of the skin comprising corneocytes, is essential for maintaining skin barrier function. Although all components of the SC are nonliving, their homeostasis is maintained through the controlled shedding of corneocytes, ensuring a constant number of layers and consistent thickness; however, the mechanisms underlying this regulation remain largely unknown. Although previous studies have suggested a neutral-to-acidic pH gradient in the SC, recent intravital imaging at single-corneocyte resolution revealed a 3-stepwise pH zonation: lower-moderately acidic, middle acidic, and upper neutral. This perspective review highlights the importance of understanding SC homeostasis using this 3-tiered pH model and emphasizes how its disruption may contribute to inflammatory skin diseases. Determination of the mechanisms that establish and maintain these pH zones offers promising insights for the development of targeted therapies.