GDF-3 (previously called Vgr-2) is a TGF-beta superfamily member belonging to the growth/differentiation factor family (1, 2). GDF-3 is expressed in undifferentiated embryonic stem (ES) cells, adipose tissue and the brain (2‑4). In ES cells, it maintains pluripotency and influences early cell fate decisions (5, 6). For example, frog embryos injected with GDF-3 develop a secondary dorsal axis and deletion of mouse GDF-3 can produce defects in the anterior visceral endoderm of the pre‑gastrulation embryo (5, 6). In adipocytes, GDF-3 is induced by a high fat diet and promotes adipogenesis (3). GDF-3 has been reported to oppose BMP’s functions and to have a nodal-like activity in early development (1). The 366 amino acid (aa) mouse GDF-3 contains a 22 aa signal sequence, a 230 aa propeptide and a 114 aa mature protein that contains one potential N-glycosylation site. Most of GDF-3 is present as the prepro form, while the mature GDF-3 is presumably the secreted, active form (1). The mature protein contains the cysteine-knot structure that is conserved throughout family members. Since it lacks the fourth cysteine, which is responsible for the formation of inter-molecular disulfide bond, GDF-3 may exist as a non-covalent homodimer. Within the pro region, mouse and human GDF-3 share 65% aa sequence identity. Among family members, mature GDF-3 is most similar to mouse BMP-6 (45% aa identity) and Xenopus VG‑1 (52% aa identity).