In patients with advanced CKD the lifespan of red blood cells (RBCs) is often shortened, a condition attributed to the ‘uremic milieu.’ We reported recently that the uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) shares structural similarities with Jedi1, a chemical activator of the mechanosensitive cation channel PIEZO1, whose activation increases calcium influx into cells. The gene discussed is PIEZO1; the disease is chronic kidney disease.