The COP9 signalosome (also known as CSN) is a highly conserved multi-subunit enzymatic complex that plays a role as the sole CRL ubiquitin ligase deneddylase. Deneddylation decreases ubiquitin ligase activity of CRL complexes, and is required for the sCAND1 binding to the cullin subunit. The CSN is required for stabilization of CRL substrate receptors: without the CSN, CRL complexes are "hyper-active" and promote their own degradation through autoubiquitination. Both the CSN and CAND1 allow remodeling of the ubiquitin ligase complex through exchange of the ubiquitin substrate specific receptors (Cope et al, 2006; Denti et al, 2006; Peth et al, 2007; Schmidt et al, 2009; Enchev et al, 2012; Pierce et al, 2013; Zemla et al, 2013; Wu et al, 2013, reviewed in Wei et al, 2008). Deregulation of the CRL-CSN pathway causes misregulation of numerous important cellular targets and has been implicated in the development of some cancers (reviewed in Gummlich et al, 2013).