VHL encodes a tumor suppressor, which possesses E3 ubiquitin activity in complex with the scaffold proteins EloB/C, Cul2 and Rox1a/Rbx1.194 In clear cell renal cell carcinoma, VHL activity is suppressed, resulting in the accumulation of the transcription factor Hif-1α in response to hypoxia.195 Hypoxia has been found to stimulate copper uptake via increasing CTR1 expression through the hypoxia-induced factor pathway.196–198 In Drosophila, we found that Vhl functions differently in different tissues, influencing melanin formation by altering copper levels via Ctr1A. Here, VHL is linked to clear cell renal carcinoma.