Proteases: common culprits in human skin disorders

Trends Mol Med. 2014 Mar;20(3):166-78. doi: 10.1016/j.molmed.2013.11.005. Epub 2013 Dec 28.


Recent findings from the clinic and the laboratory have transformed the way proteases and their inhibitors are perceived in the outermost layer of the skin, the epidermis. It now appears that an integrated proteolytic network operates within the epidermis, comprising more than 30 enzymes that carry out a growing list of essential functions. Equally, defective regulation or execution of protease-mediated processes is emerging as a key contributor to diverse human skin pathologies, and in recent years the number of diseases attributable to aberrant proteolytic activity has more than doubled. Here, we survey the different roles of proteases in epidermal homeostasis (from processing enzymes to signalling molecules) and explore the spectrum of rare and common human skin disorders where proteolytic pathways are dysregulated.

Keywords: allergy; differentiation; epidermis; homeostasis; inflammation; keratinocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation
  • Epidermis / enzymology
  • Homeostasis
  • Humans
  • Keratinocytes / metabolism
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / metabolism
  • Proteolysis
  • Skin / enzymology
  • Skin / pathology
  • Skin Diseases / enzymology*
  • Skin Diseases / pathology


  • Protease Inhibitors
  • Peptide Hydrolases