Aberrant activity of specific transporters—such as MCU complex-induced Ca2+ overload triggering mPTP opening in ischemia–reperfusion injury, VDAC1 oligomerization facilitating ROS leakage in atherosclerosis, and TRPC3/6-mediated Ca2+ influx promoting fibrosis—orchestrates hallmark features of CVDs. The gene discussed is VDAC1; the disease is atherosclerosis.