CRBN and myelodysplastic syndrome: Induced substrate degradation partially underlies the observed therapeutic efficacy of thalidomide and its derivatives in multiple myeloma4,5 and del(5q) myelodysplastic syndrome,6 as well as off-target teratogenic effects.7–9 These findings have sparked immense efforts in the field of targeted protein degradation to induce a range of substrates to CRBN for therapeutic benefit.10,11 By contrast, the endogenous substrates mediated by CRBN and how they are affected by thalidomide and its derivatives remain relatively underexplored.