This E3 ligase facilitates ubiquitination of endogenous substrates, exemplified by transcription regulator MEIS2, and when bound to thalidomide-like drugs modifies/hijacks cereblon’s substrate specificity to a different set of proteins that are then degraded (Ikaros and Aiolos: involved in IMiD efficacy in multiple myeloma, and by SALL4: involved in IMiD teratogenicity [41]). The gene discussed is CRBN; the disease is AL amyloidosis.