The key mechanism of immunomodulators used in myeloma therapy is to promote the ubiquitination of transcription factors IKAROS Family Zinc Finger 1 (IKZF1) and IKAROS Family Zinc Finger 3 (IKZF3) through the action of cereblon, an E3 ligase. The gene discussed is IKZF3; the disease is plasma cell myeloma.