Podocyte dysfunction in kidney diseases: Mechanisms and therapeutic advances

Podocytes are terminally differentiated visceral epithelial cells that form the outermost layer of the glomerular filtration barrier. Through their foot processes and slit diaphragm structures, podocytes confer selective permeability to the glomerular filtration barrier and play a critical role in maintaining kidney function. Podocyte damage is characterized by foot process effacement, loss of slit diaphragm proteins, reorganization of the actin cytoskeleton, and apoptosis, and plays a central role in the pathogenesis of proteinuric glomerular diseases such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy. This narrative review examines podocyte biology, the main molecular pathways of podocyte damage (RhoA/ROCK, TGF-β, mTOR, and oxidative stress), the clinical presentations of podocytopathies, and treatment strategies ranging from RAAS blockade, SGLT2 inhibitors, cytoskeletal stabilizers, gene therapy, to regenerative medicine approaches. By highlighting recent findings and translational challenges, the importance of podocyte-focused therapies in glomerular diseases is emphasized. Future studies aim to preserve podocyte integrity and prevent progressive kidney disease through personalized molecular therapies and multidisciplinary research.