Noggin encoded by the NOG gene, was first isolated from Xenopus, having the function of inducing secondary axis formation in frog embryos. It inhibits TGF-β family ligands and preventing them from binding to their corresponding receptors. Noggin was originally found as a BMP-4 antagonist, and then has been shown to modulate the activities of other BMPs (BMP-2, 7, 13 and 14). Additionally, it has pleiotropic effect, both in early development and later stages. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. In recent report, proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) have relation with the mutant of evolutionarily conserved amino acid residues of Noggin. Mature human Noggin shares 99 %, 99 %, 98 %, 97 % and 89 % a.a. sequence identity with mouse, rat, bovine, equine and chicken Noggin, respectively.