| Summary: | The calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR), is a cell-surface-located receptor that can induce highly diffusible messengers (IP3, Ca<sup>2+</sup>, cAMP) in the cytoplasm to activate various cellular responses. Recently, it has also been suggested that the CaSR mediates the intracellular communications between the endoplasmic reticulum (ER), mitochondria, nucleus, protease/proteasome, and autophagy–lysosome, which are involved in related cardiovascular diseases. The complex intracellular signaling of this receptor challenges it as a valuable therapeutic target. It is, therefore, necessary to understand the mechanisms behind the signaling characteristics of this receptor in intracellular communication. This review provides an overview of the recent research progress on the various regulatory mechanisms of the CaSR in related cardiovascular diseases and the heart–kidney interaction; the associated common causes are also discussed.
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