(A) In the absence of an immunomodulatory drug like thalidomide the CUL4CRBN complex (multiple colors) 'tags' a substrate (purple) for degradation by the proteasome (pale blue). SALL4 remains intact during this process and is therefore able to control the transcriptional activity of target genes to control robust embryonic limb development. (B) The presence of thalidomide results in SALL4 being tagged for degradation. The subsequent absence of SALL4 prevents the transcription of its target genes and thus likely interferes with limb development, as observed in thalidomide syndrome. iMiD: immunomodulatory drug.