The loss of profilin1 is catastrophic to podocytes.

Profilin1 belongs to a family of small monomeric actin-binding proteins with diverse roles in fundamental actin-dependent cellular processes required for cell survival. Podocytes are postmitotic visceral epithelial cells critical for the structure and function of the kidney filtration barrier. There is emerging evidence that the actin-related mode of cell death known as mitotic catastrophe is an important pathway involved in podocyte loss. In this issue of the JCI, Tian, Pedigo, and colleagues demonstrate that profilin1 deficiency in podocytes triggered cell cycle reentry, resulting in abortive cytokinesis with a loss in ribosomal RNA processing that leads to podocyte loss and glomerulosclerosis. This study demonstrates the essential role of actin dynamics in mediating this fundamental mode of podocyte cell death.