NOTCH1 and focal segmental glomerulosclerosis: Podocyte apoptosis has been shown to play an instigating role in the pathogenesis of FSGS, and Notch activation in mature podocytes induces apoptosis.28, 30 Conditional activation of the intracellular domain of Notch1 in mature podocytes is associated with positive TUNEL staining and upregulation of podocyte Trp53 and Apaf1. Pifithrin-α inhibits apoptosis in podocytes transduced with the Notch1 intracellular domain, thereby suggesting that Notch1 induces podocyte apoptosis via the p53 pathway.28