This invention relates to a novel target for production of immune and non-immune based therapeutics and for disease diagnosis. More particularly, the invention provides therapeutic antibodies against TMEM154 antigens, which are differentially expressed in cancer, and diagnostic and therapeutic usages, wherein the cancer is relates to multiple myeloma, including multiple myeloma precursor diseases. This invention further relates to extracellular domains of TMEM154 proteins and variants, and therapeutic usages thereof.