Signaling redundancy enables aPC to rescue defective insulin signaling. Scheme illustrating the compensatory mechanism through which coagulation protease aPC rescues defective insulin signaling in mouse models of DKD. The regulatory subunits of PI3Kinase p85α and p85β and sXBP1 protein complexes act as platforms that integrate signals downstream of INSR and GPCR-PAR-3. Treatment with aPC efficiently rescues insulin-signaling defect by activating p85-dependent sXBP1 nuclear translocation and restores adaptive UPR in podocytes, thereby protecting against DKD.