BMP-8, also known as osteogenic protein 2 (OP-2), was first isolated from a hippocampal library in a screen to identify relatives of BMP-7/OP-1 (1). BMPs are a family of structurally and functionally related proteins and represent a subfamily of the transforming growth factor beta (TGF-beta ) superfamily. BMPs are involved in a wide range of processes including embryogenesis, tissue morphogenesis, cell differentiation and migration, and tumorigenesis. Cellular responses to BMPs are mediated by hetero-oligomeric complexes of type I and type II serine/threonine kinase receptors (2-4). BMP-8a and BMP-8b, produced from separate genes, share 98% aa sequence identity in human but only 74% in mouse within the mature regions. Human BMP-8b is synthesized as a 402 aa precursor protein that is cleaved between Arg263 and Ala264 to release the C-terminal mature protein. Mature human BMP-8b shares 91% and 71% aa sequence identity with mouse mature BMP-8a and -8b, respectively. BMP-8a is expressed during pregnancy in the deciduum and trophoblast cells, by inner root sheath cells of developing hair follicles, and by the epididymis and spermatids (5-7). In the mouse it cooperates with BMP-7 in the maintenance of spermatogenesis but is not required for the initiation of spermatogenesis (7, 8). BMP-8b, in contrast, is required for both the initiation and maintenance of spermatogenesis (9). BMP-8a is induced during osteoblast differentiation at the onset of mineralization and during the osteogenic phase of bone repair in osteoblasts and osteocytes (10-12). BMP-8b is also highly expressed in osteosarcomas and pancreatic cancer, and it contributes to tumor progression (13, 14). BMP-8b is also expressed in adipose tissue and the hypothalamus where it contributes to the regulation of energy balance and thermogenesis (15, 16).