The Histidine-rich glycoprotein (HRG) is a relatively abundant mammalian plasma protein that is implicated in a number of different physiological and pathological processes, such as formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial, angiogenesis, coagulation and fibrinolysis.  These immunological and vascular functions are mediated through a variety of different ligand interactions and it has therefore been suggested that HRG is an adaptor molecule that is capable of assembling an arsenal of soluble ligands in concert through its multi-domain structure to assist in bridging singular or multiple biological processes.  The ability of HRG to acquire a net positive charge through coordination with metal ions or protonation of histidine residues has been shown in many cases to enhance ligand interactions, therefore providing a level of regulation that allows HRG to act as a pH-sensing molecule at sites normally associated with wound healing or tumor growth. Crystallographic studies to determine the structure of HRG would provide crucial insight into its molecular mechanism of action.  HRG undergoes a number of post-translational modifications including glycosylation, disulphide bond formation and phosphorylation sites, that have complicated the ability to produce significant amounts of functional soluble protein. This study demonstrates that using in vitro refolding methods of protein derived from the inclusion bodies of BL21 codon plus cell lines, may provided sufficient quantities of the predicted N-terminal cystatin homology domains of HRG for structural studies. Affinity purification using heparin sulfate a known ligand of these domains was exploited to select for the correctly folded isoform. These soluble HRG domains were shown to be monodispersed by size exclusion chromatography methods, and were subjected to SAXS analysis. Interestingly, these experiments revealed higher oligomeric species of the N-terminal HRG domains, however whether this oligomerisation is a natural occurrence or is artificially induced by the conditions of the buffer requires further investigation.