Calreticulin is an endoplasmic Ca²⁺ binding protein and molecular chaperone. As a cardiac embryonic gene, calreticulin is essential for heart development. The protein supports Ca²⁺-dependent signaling events that are critical to cardiomyocyte differentiation and cardiogenesis. The increased expression of calreticulin and endoplasmic reticulum/sarcoplasmic reticulum Ca²⁺ capacity produces cardiomyocytes with enhanced efficiency, and detrimental mechanical stretching of cardiac fibroblasts, leading to cardiac pathology. Deletion of the calreticulin gene in adult cardiomyocytes results in left ventricle dilation, an impaired electrocardiogram, and heart failure. These observations indicate that a well-adjusted endoplasmic reticulum and calreticulin-dependent Ca²⁺ pool in cardiomyocytes are critical for the maintenance of proper cardiac function.

Stress responses are important to human physiology and pathology, and the inability to adapt to cellular stress leads to cell death. To mitigate cellular stress and re-establish homeostasis, cells, including those in the cardiovascular system, activate stress coping response mechanisms. The endoplasmic reticulum, a component of the cellular reticular network in cardiac cells, mobilizes so-called endoplasmic reticulum stress coping responses, such as the unfolded protein response. MicroRNAs play an important part in the maintenance of cellular and tissue homeostasis, perform a central role in the biology of the cardiac myocyte, and are involved in pathological cardiac function and remodeling. In this paper, we review a link between endoplasmic reticulum homeostasis and microRNA with an emphasis on the impact on stress responses in the cardiovascular system.

Stromal interaction molecule 1 (STIM1) is a Ca²⁺ sensor in the endoplasmic reticulum (ER) membrane. The protein plays a crucial role in store-operated Ca²⁺ entry (SOCE) by transducing ER Ca²⁺ depletion signals to Ca²⁺ release-activated Ca²⁺ channel protein 1 (ORAI1) at the plasma membrane. Myotubularin related protein 7 (MTMR7) is a lipid phosphatase that dephosphorylates phosphoinositides. Using yeast two-hybrid analysis, immunoprecipitation and fluorescence microscopy, we discovered that MTMR7 interacts with STIM1 at the ER. These observations identified MTMR7 as a novel STIM1-binding protein that bridges myotubularins and phosphoinositide signaling with SOCE. Our research revealed a novel link between Ca²⁺ signaling and phosphoinositide biology, positioning MTMR7 as a potential marker or drug target for SOCE related human pathophysiology.