Grant: Project Grant

Heart Failure (HF) remains the leading cause of mortality worldwide, representing a major economic burden on the healthcare system. Although the pathophysiology of HF is not fully characterized, the role of prolonged endoplasmic reticulum (ER) stress in the development and progression of HF is well-established. The ER is the largest membrane-bound organelle that participates in a wide array of cellular processes in eukaryotic cells. Instabilities in its structure and function can lead to activation of ER-dependent cellular pathways ultimately resulting in cardiac dysfunction. Defects in ER formation and function have been shown to result in numerous related diseases including neurological hereditary spastic paraplegia, cardiac dysfunction and eventual heart failure. Therefore, proper ER formation and maintenance of ER homeostasis are critical factors for understanding the pathophysiology of ER-related diseases. While the formation of the ER is not fully understood, an important group of proteins that mediate the formation and maintenance of the ER are receptor expression enhancing proteins (REEPs). Here, we propose to investigate the role of Reep5 in muscle pathologies, including cellular ER stress and heart failure. We aim to examine the physiological role of Reep5 utilizing Reep5 conditional knockout (KO) mice. Ultimately, understanding the role of Reep5 will provide greater insights into ER-related cardiac disease.