In this study, we evaluated the potential involvement of cathepsin-mediated arterial remodeling in sickle cell disease by studying the effects of TNFα stimulation and adhesion of mononuclear cells isolated from whole blood of individuals homozygous for the sickle mutation on endothelial cell expression and activation of cathepsins K and V. We employed a novel, multiplex cathepsin zymography technique to simultaneously quantify the active forms of cathepsins K, L, S, and V in response to the different stimulation and coculture conditions [23]. Here, CTSS is linked to sickle cell disease.