Copper is an essential dietary micronutrient and disease states can arise when cytosolic levels of this metal are disrupted. To maintain homeostasis within the cell, multiple proteins transport copper in and out of the cell and between various intracellular organelles. Despite being important for human health, our understanding of how copper transport proteins are regulated at the post-translational level is currently incomplete. Using Drosophila as a model, my research is investigating the mechanisms governing the post-translational regulation of the main proteins involved in cellular copper import and export. I will present evidence of isoform-specific regulation of the copper importer Ctr1A by the E3 ubiquitin-ligase Nedd4. Additionally, I will demonstrate a completely novel role for Cul3-based Cullin-RING ligases in the post-translational regulation of copper transporters, with a recent exciting discovery indicating that Cul3 can differentially regulate proteins involved in copper import and export dependent upon interactions with certain substrate adaptors. Preliminary results will also be presented which indicate that the deubiquitinase Usp7 may have an opposing role to Cul3 in terms of regulating the copper efflux protein ATP7.