Human genetics of nephrotic syndrome and the quest for precision medicine

In this review, we take a combined membrane biologist's and geneticist's view of the podocyte, to examine how genetics have informed our understanding of membrane receptors, channels, and other signaling molecules affecting podocyte health and disease.

An integral part of the kidney, the glomerulus, is responsible for the kidney's filter function. Within the glomerulus, the podocyte is a unique cell serving a critically important role: it is exposed to signals from the urinary space in Bowman's capsule, it receives and transmits signals to/from the basement membrane upon which it elaborates, and it receives signals from the vascular space with which it also communicates, thus exposed to toxins, viruses, chemicals, proteins, and cellular components or debris that flow in the blood stream. Our understanding of how podocytes perform their important role has been largely informed by human genetics, and the recent revolution afforded by exome sequencing has brought a tremendous wealth of new genetic data to light.

Genetically defined, rare/orphan podocytopathies, as reviewed here, are critically important to study as they may reveal the next generation targets for precision medicine in nephrology.