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Gains in understanding of podocyte loss. Podocyte loss is a key element underlying glomerulosclerosis. Various mechanisms have been proposed for cell loss. These include local hemodynamic effects and local stresses on cell and hemodynamic changes, which together may contribute to detachment of podocytes, leading to sclerosis. Elegant studies based on classic observations add state-of-the-art imaging, modeling, intravital microscopy, and ultrastructural geometry analyses and provide new insights into potential mechanisms for injury and loss of this key cell.