FIGURE 1: Summary of major functions of REEP5 in cardiac myocytes. REEP5 is a SR/ER membrane protein responsible for generating high membrane curvature to stabilize the highly differentiated SR network in cardiac myocytes. Normal expression of REEP5 under healthy physiological conditions (left) is required for proper formation, maintenance, and function of the SR/ER in the myocyte; loss of REEP5 (right) results in SR membrane vacuolization, excessive intracellular ROS, hyperpolarized mitochondrial membrane potential, activated ER stress pathways, dysregulated Ca²⁺ cycles, and cardiac dysfunction.