CRBN and plasma cell myeloma: Given our previous demonstration that CUL4-DDB1-CRBN mediates ERAD of human ClC-1 channel and that over-expression of CRBN significantly suppresses ClC-1 protein level (110), it is possible that thalidomide/lenalidomide-induced muscle cramps observed in myeloma patients is in part attributable to enhanced degradation of human ClC-1 channel in skeletal muscles.