A recent work by Nolfi-Donegan et al. demonstrated that high-mobility group box 1(HMGB1), a DNA-binding protein that is released by damaged tissue and platelets, strongly enhances the ADP-P2Y12 platelet activation pathway in sickle cell disease (Nolfi-Donegan et al., 2024). The gene discussed is HMGB1; the disease is sickle cell disease.