Cullin-4A (CUL4A) is a core component of multiple cullin-RING type Ubiquitin ligase complexes that mediate the ubiquitination of proteins involved in cell cycle progression, DNA repair and other processes. In the DCX complex (DDB1-CUL4-X-box), CUL4A serves as a scaffold that organizes the DDB1-X-box substrate recognition subunits with the RBX1 subunit and contributes to catalysis through positioning of the substrate and an E2 ubiquitin-conjugating enzyme. In vivo, the E3 ubiquitin ligase activity of the DCX complex is dependent on neddylation of the CUL4 subunit, though neddylation may be dispensable in some in vitro reactions.