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.