In this study, to investigate the role and potential mechanism of endothelial cell calpain in LPS-induced renal dysfunction, we established animal models of endotoxemia in mice with endothelial-specific Capn4 knockout (KO) (TEK/Capn4−/−), mice with calpastatin overexpression (Tg-CAST) and mice with myeloid-specific Capn4 knockout (LYZ/Capn4−/−), and we established an in vitro model using pulmonary microvascular endothelial cells (PMECs). Here, CAST is linked to serum lipopolysaccharide activity.