The myeloma cell line, MM1.S, produces high amounts of dysfunctional immunoglobulins (paraproteins); treatment with the immunomodulatory drug (IMiD) LEN and the 26S proteasome inhibitor BTZ results in accumulation and aggregation of intracellular misfolded proteins, ultimately leading to cell apoptosis (Fig. 2a)5,46–49. Here, CASC3 is linked to plasma cell myeloma.