Complement component 4 is a protein involved in the complement system.It is cleaved into proteins 4a and 4b. C4d is the degradation product of the activated complement factor C4, a component of the classical complement cascade which is typically initiated by binding of antibodies to specific target molecules.

Following activation and degradation of the C4 molecule, thio-ester groups are exposed which allow transient, covalent binding of the degradation product C4d to endothelial cell surfaces and extracellular matrix components of vascular basement membranes near the sites of C4 activation. C4d is also found in intracytoplasmic vacuoles of endothelial cells. Covalent binding renders C4d a stable molecule that can easily be detected by immunohistochemistry. Detection of C4d is regarded as an indirect sign, a ‘footprint’ of an antibody response.