The link between cathepsin C and NET formation has been demonstrated in studies of Papillon-Lefèvre syndrome (PLS), which results from inactivating mutations in cathepsin C. In patients with PLS, there is a lack of typical azurophilic granule proteases, including NE, cathepsin G, and PR3, leading to impaired NET formation in response to ROS [121,122]. Here, ELANE is linked to Papillon-Lefevre disease.