The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7–10]. The gene discussed is TLR4; the disease is Schnyder corneal dystrophy.