CTSS and type 2 diabetes mellitus: Although increased urinary activities of cathepsins have been observed and proposed as early markers of DN [46, 47], including cathepsins B, D, and K in the urine of T2DM or diabetic kidney disease [47, 48], cathepsin E appears to decrease, showing a significant trend in the macroalbuminuric group of DN patients [49], implying divergent regulatory roles in diabetic complications.