Accessible skin proteins

Accessible skin proteins refers to the collective group of proteins located in the outermost layers of the skin, primarily the stratum corneum and viable epidermis, which are readily available for interaction with topically applied substances (AOP Wiki, 2023). This group includes structural proteins such as keratins (e.g., Keratin 1, 5, 10, and 14), filaggrin, and loricrin, as well as extracellular matrix proteins like collagen and elastin in the deeper layers (UniProt, 2024). In the context of pharmacology and toxicology, these proteins are critical as the primary site for the Molecular Initiating Event (MIE) of skin sensitization, where electrophilic chemicals (haptens) covalently bind to nucleophilic residues like cysteine or lysine to form complete antigens (OECD, 2014). Additionally, these proteins are targeted by keratolytic agents such as salicylic acid to treat hyperkeratotic conditions and are utilized in drug delivery strategies to create reservoirs that prolong the local residence time of topical therapeutics (StatPearls, 2023; PubMed, 2018). Understanding the interaction between drugs and these accessible proteins is essential for predicting skin sensitization potential and optimizing the efficacy of dermatological treatments.

Other names

Epidermal proteinsStratum corneum proteinsSkin-binding proteinsHapten-binding proteinsDermal proteins

Covalent binding (haptenation), Keratolysis, Protein denaturation, and Drug reservoir formation