Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of iron metabolism genes. The E3 ubiquitin ligase complex comprising the F-box/LRR-repeat protein 5 (FBXL5) protein, S-phase kinase-associated protein 1 (SKP1), cullin 1 (CUL1) and NEDD8. NEDD8 (Neddylin, Neural precursor cell expressed developmentally down-regulated protein 8) is a ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. NEDD8 covalently attachs to cullins (eg CUL1) and activates their associated E3-ubiquitin ligase activity thus promoting polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins (Hori et al. 1999).