Cullin-RING ligases (CRLs) complexes participate in the regulation of diverse cellular processes, including cell cycle progression, transcription, signal transduction and development (PMID: 21816341)(PMID: 21554755). Serving as the scaffold protein, cullins are crucial for the assembly of ligase complexes, which recognize and target various substrates for proteosomal degradation. Two cullin 4 (CUL4) proteins, CUL4A (87 kDa) and CUL4B(104 kDa), are two members in cullin family with 83% of identity. Mutations in human CUL4B are one of the major causes of X-linked mental retardation. Cul4b knockout mice demonstrated that CUL4B is indispensable for embryonic development in the mouse (PMID: 22606329).