Copper (Cu) is an essential micronutrient for all eukaryotes because it participates as a redox active cofactor in multiple biological processes, including mitochondrial respiration, photosynthesis, oxidative stress protection, and iron (Fe) transport. In eukaryotic cells, Cu transport toward the cytoplasm is mediated by the conserved CTR/COPT family of high-affinity Cu transport proteins. This outlook paper reviews the contribution of our research group to the characterization of the function played by the Arabidopsis thaliana COPT1–6 family of proteins in plant Cu homeostasis. Our studies indicate that the different tissue specificity, Cu-regulated expression, and subcellular localization dictate COPT-specialized contribution to plant Cu transport and distribution. By characterizing lack-of-function Arabidopsis mutant lines, we conclude that COPT1 mediates root Cu acquisition, COPT6 facilitates shoot Cu distribution, and COPT5 mobilizes Cu from storage organelles. Furthermore, our work with copt2 mutant and COPT-overexpressing plants has also uncovered Cu connections with Fe homeostasis and the circadian clock, respectively. Future studies on the interaction between COPT transporters and other components of the Cu homeostasis network will improve our knowledge of plant Cu acquisition, distribution, regulation, and utilization by Cu-proteins. 1. Introduction Copper (Cu) functions as a redox active cofactor in a wide variety of plant proteins including plastocyanin, cytochrome c oxidase, Cu/Zn-superoxide dismutase (Cu/Zn-SOD), ethylene receptors, laccases, ascorbate and amine oxidases, plantacyanin, and polyphenol oxidases. Consequently, Cu is essential for fundamental biological processes in plants including photosynthesis, mitochondrial respiration, oxidative stress protection, cell wall metabolism, ethylene perception, response to pathogens, and molybdenum cofactor biosynthesis [1–3]. The optimal endogenous Cu levels in plants can substantially range depending on the species and its environmental availability. Adequate Cu levels in vegetative tissues are around 6？μg/g dry weight, with levels below 5？μg/g leading to deficiency symptoms [4]. Cu deficiency defects in plants include a general reduced growth rate, chlorosis, especially in young leaves, curling of leaf margins, damage at the apical meristem, defects in cell wall formation, and lignification, which causes insufficient water transport, defective pollen development and viability, limited fruit formation, and diminished seed production and viability [4]. Plant Cu availability also depends on
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