In support of our hypothesis, the results of the present study demonstrated for the first time that a RAGE blockade (1) dampened kidney damage, as evidenced by reduced glomerular hypertrophy, interstitial fibrosis, iron deposition, and KIM-1 protein expression in SS mice; (2) reduced the activation of both NADPH oxidase and NF-κBp65 acting downstream of the AGE/RAGE signaling pathway; (3) increased hematocrit, RBC count, and hemoglobin level, and decreased reticulocyte count and sickle cell count in SS mice. Here, HAVCR1 is linked to synovial sarcoma.