This study aimed to develop a targeted peptide to disrupt the IP<sub>3</sub>R-GRP75-VDAC1 complex and evaluate its therapeutic efficacy in atherosclerosis.<h4>Methods</h4>Based on structural and interface analyses of the IP<sub>3</sub>R-GRP75 complex, we designed cell-permeable MAM-targeting peptides. The gene discussed is VDAC1; the disease is atherosclerosis.