The micronutrient copper powers many essential biological processes. However, poor management of cellular copper levels can lead to severe pathologies, such as cancer and neurodegeneration. Large Cu(I) elevations potently inhibit ubiquitination by affecting the function of both ubiquitin itself and the proteasome. Conversely, moderate Cu(I) supplementation instead promotes polyubiquitination. The E2 enzyme UBE2D2 contributes to this effect by binding copper with sub-femtomolar affinity, undergoing conformational changes, and promoting the ubiquitination of various substrates. It may be that UBE2D2 acts as a copper sensor, helping cells maintain homeostasis. My work further examines the in vivo relationship between copper and UBE2D2, using the fruit fly, Drosophila melanogaster, as a model. RNAi knockdown of the fly UBE2D2 ortholog UbcD1 results in severe neuronal and epithelial cell defects. Introduction of a human UBE2D2 construct can ameliorate these phenotypes. To assess the importance of key copper-binding residues of UBE2D2 for its function, I also developed several human UBE2D2 mutant constructs and performed in vivo rescue experiments of UbcD1 knockdown phenotypes. Using both phenotypic and molecular analyses, I have also established several novel functions of Drosophila UbcD1, including the regulation of copper transport and p53-dependent apoptosis, and assessed the importance of copper-binding for these functions. These results demonstrate clear links between copper, ubiquitination, and apoptosis, with UbcD1 as a central regulator. As these pathways are strongly connected to both cancer and neurodegeneration, this fruit fly model brings us closer to understanding how this pathway allows cells to manage stress in both healthy and disease states.