Molecular pathophysiology of podocyte function

The ability of the visceral epithelial cells of the glomerulus, podocytes, to form foot processes with unique intercellular connection, the slit diaphragm, reflects a highly differentiated organization which plays a crucial role in the glomerular filtration barrier. With the recent molecular findings, the podocyte now is emerging as a key cell involved in glomerular damage.

Indeed, recent genetic studies of human familial cases of nephrotic syndromes and focal segemental glomerulosclerosis (FSGS) and genetically-modified animal models have led to the identification of new podocyte proteins and highlighted the crucial role of podocyte proteins. Positional cloning has allowed the identification of the ACTN4-gene, encoding the podocyte actin binding protein a-actinine 4, as the causative gene in some cases of autosomal dominant FSGS. This strategy has also led to the cloning of the NPHS1- and NPHS2-genes, encoding nephrin, and podocin, respectively.