Proteolytic fragmentation of ECM proteins by secreted proteases controls their localisation, activation, and interaction, adding an additional layer of regulation for tissue processes. Using experimental data, databases/algorithms such as MEROPS and PROSPER have been created to calculate probability matrices for target protease sequences.98–100 This is a valuable resource for research and is particularly useful when used in conjunction with proteomics. Standard proteomics pipelines work with digested protein mixtures (i.e. trypsin digestion) to screen for the abundance of proteins in a tissue. Trypsin cleaves C-terminally to lysine (Lys, K) or arginine (Arg, R) residues. However, proteases other than trypsin can be present in samples and the endogenous proteolytic activity may give rise to non-tryptic peptides. In a study from Stegemann et al.59, we described a number of potential proteolytic targets for various MMPs in the vasculature after addition of these proteases to human vascular tissue explants.