BACKGROUND: The skin is the largest organ in the human body and serves as a multilayered protective shield from the environment as well as a sensor and thermal regulator. However, despite its importance, many details about skin structure and function at the molecular level remain incompletely understood. Recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics have enabled the quantification and characterization of the proteomes of a number of clinical samples, including normal and diseased skin.

SUMMARY: Here, we review the current state of the art in proteomic analysis of the skin. We provide a brief overview of the technique and skin sample collection methodologies as well as a number of recent examples to illustrate the utility of this strategy for advancing a broader understanding of the pathology of diseases as well as new therapeutic options. Key Messages: Proteomic studies of healthy skin and skin diseases can identify potential molecular biomarkers for improved diagnosis and patient stratification as well as potential targets for drug development. Collectively, efforts such as the Human Skinatlas offer improved opportunities for enhancing clinical practice and patient outcomes.