Voegeli R, et al. - This study encompassed the elucidation of the stratum corneum (SC) proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post auricular (PA) site, with the intent of yielding new molecular targets for the treatment of photoaged skin. The photodamaged facial SC revealed clear examples of poor keratinocyte differentiation and associated metabolic and signalling pathways together with reduced SC maturation. The assumption put forth was that there existed a poor crosstalk between the keratinocyte endoplasmic reticulum unfolded protein response (UPR), proteasome network and autophagy machinery which possibly caused impaired keratinocyte proteostasis. Superimposed on these aberrations was an apparently enhanced target of rapamycin (mTOR) pathway leading to reduced SC formation and maturation. A corneocyte scaffold disorder existed in the photodamaged cheek SC.