Myeloma cells produce factors that increase osteoclasts, the cells that destroy bone. Many of these factors work by activating specific genes using NFkB, a signaling factor, which induces gene activity. In this proposal, we will characterize the role of a recently identified member of the NFkB signaling pathway, p62ZIP, in osteoclast formation and myeloma cell growth, and determine if blocking p62ZIP or deleting the p62ZIP gene in mice decreases osteoclast formation and the capacity of cells from these mice to support the growth of myeloma cells.