C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway (AP) of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both C3GN and DDD are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy, DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known.We performed laser microdissection of glomeruli followed by mass spectrometry in 12 known cases of DDD and C3GN each to determine the proteomic profile and differences between C3GN and DDD.