The mechanism of copper homeostasis and its role in disease

Abstract Copper (Cuprum) is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism. Emerging evidence has demonstrated the role of copper in angiogenesis and cellular signaling. Moreover, raised copper levels have been detected in hepatocellular carcinoma and other cancers. An inherited or acquired copper imbalance, including inadequately low or excessively high copper levels, as well as inappropriate copper distribution in the body, is implicated in a number of diseases. In addition, a recent groundbreaking study identified a copper‐induced type of programmed cell death named cuprotosis, the mechanism of which greatly deferred from that of other known cell death modes. The first part provides an overview of the regulation of copper homeostasis and discusses the underlying mechanisms of cuprotosis. In the second part, the authors focus on the functions of copper in liver diseases and other metabolic disorders, before discussing how this knowledge could contribute to the development of effective targets to treat such diseases.