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For several decades, it has been thought that the glomerular basement membrane (GBM) provides a charge-selective barrier for glomerular filtration. However, recent evidence has presented challenges to this concept: selective removal of heparan sulfate (HS) moieties that impart a negative charge to the GBM causes little if any increase in proteinuria. Removal of agrin, the major GBM HS-proteoglycan (HSPG), from the GBM causes a profound reduction in the glomerular anionic charge without changing the excretion of a negatively charged tracer. Perlecan is another HSPG present in the GBM, as well as in the mesangium and Bowman's capsule, that could potentially contribute to a charge barrier in the absence of agrin.

Glomerular filtration is normal in the absence of both agrin and perlecan–heparan sulfate from the glomerular basement membrane