Hence, maintaining sGC heme in the ferrous state is essential for sGC-cGMP signaling via NO and sGCstim, whereas sGCact can act independently of the ferrous heme group, bound to the β1 subunit (encoded by GUCY1B1), potentially explaining higher sGCact activity under pathophysiological and high oxidative stress conditions, such as DKD, compared with sGCstim.14 The gene discussed is SGCB; the disease is diabetic kidney disease.