Copper is an essential trace element involved in numerous physiological processes, including mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Dysregulation of copper homeostasis, whether due to excess or deficiency, has been implicated in various health problems, including atherosclerosis. The concept of copper-induced cell death, termed cuproptosis, has emerged as a novel mechanism contributing to atherosclerosis. This review provides an overview of copper metabolism, summarizes evidence linking copper dyshomeostasis to atherosclerosis, and discusses the mechanisms underlying atherosclerosis development in terms of both copper excess and deficiency. It also explores the evidence for and mechanisms of cuproptosis, its interactions with other modes of cell death, and the role of cuproptosis-related mitochondrial dysfunction in atherosclerosis. Finally, it explores therapeutic strategies targeting this novel form of cell death to manage atherosclerosis. Copper metabolism involves absorption, storage, transportation, and elimination. Copper is primarily absorbed in the small intestine and transported to the liver, where it is stored and excreted. Copper homeostasis is tightly regulated by copper transporters and chaperones, ensuring proper distribution and function within cells. Copper is essential for various cellular processes, including energy metabolism, antioxidant defense, and neurotransmitter synthesis. However, both excess and deficiency of copper can lead to cytotoxicity and pathological alterations. Evidence suggests that copper dyshomeostasis contributes to atherosclerosis through mechanisms such as oxidative stress, inflammation, endothelial dysfunction, and lipid metabolism. Copper excess can increase oxidative stress, promote lipid peroxidation, and impair antioxidant defenses, while copper deficiency can reduce the activity of antioxidant enzymes and increase oxidative stress. These processes contribute to the development and progression of atherosclerosis. Cuproptosis, a copper-dependent form of cell death, involves the aggregation of lipoylated mitochondrial proteins, disrupting the TCA cycle and interfering with cellular energy production. Cuproptosis is distinct from other forms of cell death and is closely associated with mitochondrial dysfunction. The interaction between cuproptosis and other cell death pathways, such as pyroptosis, necroptosis, and ferroptosis, is also discussed. Therapeutic strategies targeting cuproptosis include the use of copper chelators, regulation of copper chaperone protein expression, and the use of copper ionophores. Copper chelators such as TTM and EDTA have shown potential in reducing atherosclerosis progression by modulating copper-related pathways. Regulation of copper chaperone proteins, such as ATOX1, may offer alternative approaches to control copper levels and limit copper-induced cell death. Copper ionophores, such as elesclomol, have been investigated for their potential in targeting copper-induced cell death. In conclusion, copper plays a complex role in atherosclerosis, influencing various physiological processes and contributing to the development and progression of the disease. Understanding the mechanisms of copperCopper is an essential trace element involved in numerous physiological processes, including mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Dysregulation of copper homeostasis, whether due to excess or deficiency, has been implicated in various health problems, including atherosclerosis. The concept of copper-induced cell death, termed cuproptosis, has emerged as a novel mechanism contributing to atherosclerosis. This review provides an overview of copper metabolism, summarizes evidence linking copper dyshomeostasis to atherosclerosis, and discusses the mechanisms underlying atherosclerosis development in terms of both copper excess and deficiency. It also explores the evidence for and mechanisms of cuproptosis, its interactions with other modes of cell death, and the role of cuproptosis-related mitochondrial dysfunction in atherosclerosis. Finally, it explores therapeutic strategies targeting this novel form of cell death to manage atherosclerosis. Copper metabolism involves absorption, storage, transportation, and elimination. Copper is primarily absorbed in the small intestine and transported to the liver, where it is stored and excreted. Copper homeostasis is tightly regulated by copper transporters and chaperones, ensuring proper distribution and function within cells. Copper is essential for various cellular processes, including energy metabolism, antioxidant defense, and neurotransmitter synthesis. However, both excess and deficiency of copper can lead to cytotoxicity and pathological alterations. Evidence suggests that copper dyshomeostasis contributes to atherosclerosis through mechanisms such as oxidative stress, inflammation, endothelial dysfunction, and lipid metabolism. Copper excess can increase oxidative stress, promote lipid peroxidation, and impair antioxidant defenses, while copper deficiency can reduce the activity of antioxidant enzymes and increase oxidative stress. These processes contribute to the development and progression of atherosclerosis. Cuproptosis, a copper-dependent form of cell death, involves the aggregation of lipoylated mitochondrial proteins, disrupting the TCA cycle and interfering with cellular energy production. Cuproptosis is distinct from other forms of cell death and is closely associated with mitochondrial dysfunction. The interaction between cuproptosis and other cell death pathways, such as pyroptosis, necroptosis, and ferroptosis, is also discussed. Therapeutic strategies targeting cuproptosis include the use of copper chelators, regulation of copper chaperone protein expression, and the use of copper ionophores. Copper chelators such as TTM and EDTA have shown potential in reducing atherosclerosis progression by modulating copper-related pathways. Regulation of copper chaperone proteins, such as ATOX1, may offer alternative approaches to control copper levels and limit copper-induced cell death. Copper ionophores, such as elesclomol, have been investigated for their potential in targeting copper-induced cell death. In conclusion, copper plays a complex role in atherosclerosis, influencing various physiological processes and contributing to the development and progression of the disease. Understanding the mechanisms of copper