CSN3 is one of eight subunits (CSN1 to 8) of the highly conserved COP9 signalsome (CSN) complex originally identified as a regulator of light-mediated development in Arabidopsis. Characterization of CSN from yeast to mammals reveals its function as a modulator of signal transduction pathways involved in a variety of cellular and developmental processes. One of the major functions of the CSN is the regulation of protein degradation via intersection with the ubiquitin-proteasome pathway and regulation of E3-ubiquitin ligases. The CSN also possesses kinase activity. CSN3 is the kinase associated with the CSN complex that phosphorylates signal transducers such as I-kappa-Balpha, p105, and c-Jun. Human CSN3 maps to the Smith-Magenis syndrome locus. Microdeletions in this locus results in mental retardation, skeletal abnormalities, sleep disorder, and neurobehavior anomalies.