The paper provides a comprehensive review of endoplasmic reticulum (ER) stress-mediated cell death in cardiovascular diseases. ER stress can trigger various modes of cell death through the unfolded protein response (UPR) signaling pathway. The UPR serves as an adaptive response to restore ER homeostasis, but prolonged ER stress can lead to terminal UPR activation and cell death. The paper discusses the mechanisms of ER stress and UPR in common cardiovascular diseases, including hypertension, atherosclerosis, and heart failure, and explores potential therapeutic strategies. Key signaling pathways such as IRE1α, PERK, and ATF6 are highlighted, along with their roles in regulating autophagy, apoptosis, ferroptosis, pyroptosis, and necroptosis. The paper also reviews the involvement of other molecular chaperones like HSP70 and HSP90 in cardiovascular disease. Finally, it emphasizes the potential of targeting ER stress for treating cardiovascular diseases and outlines future research directions.The paper provides a comprehensive review of endoplasmic reticulum (ER) stress-mediated cell death in cardiovascular diseases. ER stress can trigger various modes of cell death through the unfolded protein response (UPR) signaling pathway. The UPR serves as an adaptive response to restore ER homeostasis, but prolonged ER stress can lead to terminal UPR activation and cell death. The paper discusses the mechanisms of ER stress and UPR in common cardiovascular diseases, including hypertension, atherosclerosis, and heart failure, and explores potential therapeutic strategies. Key signaling pathways such as IRE1α, PERK, and ATF6 are highlighted, along with their roles in regulating autophagy, apoptosis, ferroptosis, pyroptosis, and necroptosis. The paper also reviews the involvement of other molecular chaperones like HSP70 and HSP90 in cardiovascular disease. Finally, it emphasizes the potential of targeting ER stress for treating cardiovascular diseases and outlines future research directions.