PLAT and Hepatic fibrosis: Besides its protease activities, we and others, using the above-mentioned non-enzymatic tPA, have shown that tPA acts as a cytokine triggering multiple signal pathways to regulate various cellular processes [12,13,14,15,16] and is involved in the pathogenesis of numerous disease models, including liver fibrosis, ischemic brain injury, and chronic kidney disease [8,11,17,18].