IMiDs alter the target specificity of the CUL4A-DDB1-Cereblon E3 ubiquitin ligase (179), and in myeloma, this leads to the degradation of two key plasma cell transcription factors, Ikaros (IKZF1) and Aiolos (IKZF3) (180, 181) (Figure 4). Here, IKZF3 is linked to plasma cell myeloma.