For example, thalidomide and its derivatives have been developed to target cereblon, a DCAF of CRL4, for the treatment of multiple myeloma and other malignancies.53,54 Although further experiments are necessary to identify which DCAFs specifically recruit spastin for poly-ubiquitination, we can now capitalize on the evidence provided on the role of CRL4 to identify those substrate receptors that work together with CRL4 in the poly-ubiquitination of spastin. Here, SPAST is linked to plasma cell myeloma.