Schematic representation of the CLR4^CRBN complex in myeloma cells. IMiDs bind to CRBN, a substrate receptor protein for the CRL4A E3 ubiquitin ligase complex, and cause proteasomal degradation of IKZF1, IKZF3, and CSNK1A1 consecutively downregulating IRF4 and Myc and resulting in MM-associated cytotoxicity. The blue boxes indicate the 2 E2 ubiquitin-conjugating enzymes, UBE2D3 and UBE2G1, reported by Sievers et al as essential for lenalidomide-dependent CRL4^CRBN function in MM.