The COMMD proteins are a conserved family of proteins with central roles in intracellular membrane trafficking and signalling. A hallmark feature of all COMMD proteins is a highly conserved C-terminal region, known as the COMM domain, while the N-terminal domains of the ten human COMMD proteins are more variable in sequence and may ascribe unique functions. Previously we have shown the high resolutions structures of the individual domain of these proteins as well as a low resolution SAXS profile of the full-length proteins. This reveal several unique properties, including the necessity of COMMD protein dimer formation1. However, it is known these COMMD proteins do not function individually and are able to form oligomeric complexes with each other. In turn these oligomers associate with two coiled-coil proteins called CCDC22 and CCDC93 to form a larger assembly called the CCC complex that is critical for mediating the transport of several transmembrane cargos. Here we have co-expressed all ten human COMMD proteins using a single polycistronic E. coli expression vector, and show that they assemble into two distinct sub-complexes containing specific COMMD subunits. The X-ray crystallographic structure of one of these sub-complexes reveals an intimately assembled hetero-tetramer, primarily mediated by the c-terminal COMM domains. This work significantly advances our understanding of how the highly conserved COMMD proteins are functionally assembled.