These include coronary artery disease and chronic kidney disease, where RBC eNOS is decreased,8,59,60 hematologic diseases and hemoglobinopathies, which are characterized by a systemic decrease in NO bioavailability and defects in eNOS signaling, like in sickle cell disease.61 Moreover, our data and models may also help understanding how RBC eNOS signaling affects RBC function, NO scavenging, NO/sulfide cross-talk, and oxygen transport62 and may enable us to refine the criteria for blood banking and transfusion.63 Here, NOS3 is linked to hematologic disorder.