CRL4B can catalyze polyubiquitination of substrate proteins for proteasomal degradation as well as monoubiquitination of H2AK119 for transcriptional repression.13 Mutations in the human CUL4B gene are a common cause of X-linked mental retardation syndrome.14,15 Patients with CUL4B mutations manifest mental retardation, short stature, brachydactyly, and central obesity, suggesting a potential role of CUL4B in the regulation of adipogenesis and osteogenesis and their balance. This evidence concerns the gene CUL4B and X-linked syndromic intellectual disability.