As reviewed above, BH4 deficiency is a common cause of eNOS uncoupling in many cardiovascular diseases (Figure 5) (Vasquez-Vivar et al., 1998; Wever et al., 1997; Soltis and Cassis, 1991; Hong et al., 2001; Landmesser et al., 2003; Lee et al., 2009). Here, NOS3 is linked to cardiovascular disorder.