A new class of drugs that inhibit a pathway in multiple myeloma cells called the proteasome has proved amazingly effective in chemotherapy and stem cell transplant refractory patients. It is not clear, however, how these drugs work. We have cloned a new gene, XBP-1, that is vital for the development of plasma cells/multiple myeloma cells, and we believe that this new class of drugs might be working via XBP-1. This proposal is designed to test this idea. Knowledge gained by these experiments should aid in the discovery and development of new agents for the successful treatment of multiple myeloma.