CTSS and cystic fibrosis: This has made the cathepsin family of proteins an area of focus in CF research, as the air surface liquid (ASL) is acidic in CF patients due to a reduction in physiologic CFTR-mediated bicarbonate secretion [21]; this acidity has the doubly problematic effect of inhibiting bacterial killing per se, via downregulation of cationic antimicrobial peptides [22], as well as excessively activating proteases such as neutrophil elastase and cathepsin proteases [23].