COCO, also known as DAND5, Dante, and CKTSF1B3, is a member of the DAN domain family of BMP antagonists that includes DAN (DAND1), Gremlin/Drm (DAND2), PRDC (Protein Related to Dan and Cerberus; DAND3), and Cerberus (DAND4). DAN family members contain a cysteine knot domain that is homologous to that found in other TGF­β superfamily ligands such as BMPs that play important roles in tissue morphogenesis and developmental processes. COCO has eight Cys residues in the cysteine knot which places it in the CAN (or eight­membered ring) subfamily of BMP antagonists along with the other DAN family proteins. In Xenopus embryos, COCO is expressed by pluripotent ectodermal cells. Expression is abruptly downregulated prior to gastrulation, and the loss of ectodermal cell pluripotency is coincident with COCO downregulation. COCO is required for Xenopus left­right axis formation. It functions predominantly on the right side of the embryo, although it is equally expressed on both left and right sides. COCO binds and inhibits activin, BMP­4, GDF3/derrière, Wnt8, and Xnr1. In mouse, COCO expression is elevated on the right side of Henson’s node at the early somite stage, in contrast to the left side expression of Nodal.