It is thought that C4 glomerulopathy is the result of the activation of immune complex glomerulonephritis or lectin pathway of the complement.

• The generation of the classical pathway of complement occurs by the immune complex.
• Immune complex glomerulonephritis, such as lupus, frequently activates the classical pathway by binding C1q to the antibody-containing immune complexes, which can result in glomerular deposition of immunoglobulins, C3, C1q, and C4d.
• C4 activation can also ensue by the lectin pathway of complement.
• In the lectin pathway, mannose-binding lectins bind to mannose located on the carbohydrates structure or microbial membranes, which activate C4 (and therefore bypass C1q), resulting in the formation of the classical pathway C3 convertase.
• Glomerular C4d, is a split creation of C4, is suggestive of C4 activation as a result of activation of either the lectin pathway of the classical complement pathway.
• In C4 glomerulopathy, bright streak for C4d indicates mesangial/capillary wall deposits. C4d deposits are present in a few cases of IgA nephropathy and post-streptococcal glomerulonephritis^{[1][2][3][4][5]}.