Podocytes

Podocytes, also known as visceral epithelial cells of the glomerulus, are highly specialized cells that wrap around the capillaries of the renal glomerulus. Each podocyte has a cell body, primary processes, and interdigitating foot processes that extend to wrap the capillary tuft.

The foot processes form filtration slits bridged by slit diaphragms, a complex of proteins including nephrin, NEPH1 and NEPH2, podocin, and CD2AP. These structures are supported by a dynamic actin cytoskeleton and anchor to the glomerular basement membrane via integrins. The slit diaphragm is essential for the size- and charge-selective barrier that restricts protein passage from blood into the urinary space.

In the glomerular filtration barrier, podocytes cooperate with glomerular endothelial cells and the basement membrane to prevent protein loss while allowing water and small solutes to pass. Podocytes also secrete vascular endothelial growth factor (VEGF-A), which helps maintain the adjacent endothelium. Their injury or effacement disrupts the barrier and increases proteinuria.

Developmentally, podocytes originate from nephron progenitor cells during nephrogenesis and become postmitotic; they have limited regenerative capacity. Loss of podocytes is a hallmark of many glomerular diseases and correlates with progression to glomerulosclerosis.

Genetic mutations affecting podocyte proteins—most notably NPHS1 (nephrin) and NPHS2 (podocin)—cause congenital nephrotic syndrome or childhood nephrotic syndromes. Acquired conditions such as diabetic nephropathy and focal segmental glomerulosclerosis involve podocyte injury, foot process effacement, and detachment. Understanding podocyte biology remains central to therapies targeting proteinuria and glomerular diseases.