Schematic representation of the role of podocyte secreted Angtpl4 in the pathogenesis of minimal change disease. Sequence of events arranged from top to bottom. Podocytes secrete neutral and high pI ANGPTL4 that binds to the glomerular basement membrane (GBM) to alter protein-protein interactions, resulting in proteinuria. Over time, ANGPTL4 reaches up to the endothelial (Endo) surface. Progressive accumulation and clustering of ANGPTL4 in the GBM likely activates signals at the podocyte-GBM interface and induces foot process effacement. Circulating ANGPTL4 secreted from other organs in disease states, e. g. adipose tissue, forms medium and high order oligomers that are bound to high-density lipoprotein (HDL) particles, migrate at neutral or low-neutral pI, and do not enter the GBM or cause proteinuria. Reproduced from Clement et al9.