Despite the wealth of structural and functional information on C4BP, it is clear that several aspects of C4BP biology and regulation under normal conditions and in the acute-phase response remain unresolved. Studies to identify which interleukin and cytokines regulate C4BP expression (both α-and β-chains) are underway in our laboratory. In addition, upstream cis-acting regulatory sequences need to be characterized to attempt to correlate structural regulatory elements with expression. C4BP is a unique macromolecular protein and the mechanisms involved in controlling intracellular assembly also will be of interest. Finally, the modest increase of C4BP in SLE suggests dysregulation of altered cytokine responses in these individuals. Further studies in this and other autoimmune diseases should aid in understanding our present findings and may help in understanding C4BP gene regulation.