Human loss-of-function mutations in DPP-1 in Papillon-Lefèvre syndrome subjects markedly reduce NSP protein and proteolytic activities (active NE/PR3 < 5%; active CatG < 1%) in mature blood neutrophils [10], demonstrating that DPP-1 is a key regulator of NSP activation in humans [8]. Here, CTSC is linked to Papillon-Lefevre disease.