The endoplasmic reticulum cavity is a unique cell compartment capable of active Ca2+ transport, which is the compartment with the highest intracellular Ca2+ concentration. Under normal physiological conditions, Ca2+ is absorbed into the lumen of the endoplasmic reticulum by the cytoplasm through the calcium pump on the endoplasmic reticulum membrane, and is released into the cytosol by the IP3R and RyR channels, thereby maintaining the stability of free Ca2+ in the endoplasmic reticulum. Due to its protein folding and transport function, the endoplasmic reticulum has a large number of Ca2+-dependent molecular chaperones, such as calcium reticulin and glucose-regulated protein 78. The endoplasmic reticulum must strictly control Ca2 + levels to avoid Ca2+ imbalance leading to cell death. In addition, the endoplasmic reticulum plasma membrane (PM) acts as a barrier to free diffusion throughout the cell, connecting different organelles through a series of contact sites. A growing body of research indicates that ER-PM contact sites play an important role in maintaining Ca2+ homeostasis, signaling, and lipid regulation.