When applied to investigate the possible effects of deoxy activation of PIEZO1 in sickle cell reticulocytes, the model predicted a rapid hyperdense collapse with a much-reduced RBC lifespan, reminiscent of that documented for irreversibly sickled cells, the cells responsible for microvascular occlusion and organ failures, the major trigger of all downstream effects in sickle cell disease (5,28,73,74). This evidence concerns the gene PIEZO1 and sickle cell disease.