Why has the GBM been largely ignored?
Perhaps the answer is that it is more difficult to conceptualize the existence of restrictive pores within the GBM, which is an acellular, extracellular matrix layer organized into 3 layers — the lamina densa, lamina rara interna, and lamina rara externa (Figure 2, A and B). Like all basement membranes (or basal lamina), the GBM is composed of glycoproteins (laminins, type IV collagen, entactin/nidogen) and proteoglycans (agrin, perlecan). The lamina densa is a relatively homogeneous-appearing extracellular matrix layer, whereas the laminae rarae are less dense and contain the anionic sites defined by cationic probes. The GBM has been assumed to have the properties of a viscous gel in which the limiting pores cannot be directly visualized. On the other hand, the slit diaphragms that bridge the filtration slits are actually specialized cell junctions with properties of shallow adherens junctions that differentiate from typical junctional complexes during glomerular development (13). Lik
