The COP9 signalosome is an eight-subunit protein complex that regulates protein ubiquitination and protein turnover in a variety of plant developmental and physiological contexts, including light-regulated development, hormone signaling, and defense against pathogens. In all eukaryotes tested, the COP9 signalosome is able to posttranslationally modify the cullin subunit of E3-ubiquitin-ligase complexes by cleaving off the covalently coupled peptide, Nedd8. Two contrasting models ascribe stimulatory or inhibitory roles to the modification of cullin/E3 that is mediated by the COP9 signalosome. There is considerable disagreement as to whether Nedd8 cleavage underlies all of the COP9 signalosome's numerous cellular and phenotypic effects. This is because macroscopic phenotypes do not always correlate with biochemical defects in COP9 signalosome mutants. Additional biochemical activities, including protein interactions with the cellular machineries for protein phosphorylation, protein turnover, and protein translation, have been proposed to account for the role of the COP9 signalosome in development and disease.