Interest in the protective role of HPX has rapidly increased during the past 5 years because the causative role of heme in the pathophysiology of sepsis, sickle cell disease (SCD), other hemolytic conditions and also in atherosclerosis (Balla et al., 1991a; Nagy et al., 2010) has become accepted (Larsen et al., 2010; Smith, 2011a,b; Ghosh et al., 2013; Schaer et al., 2013; Smith, 2013; Belcher et al., 2014; Schaer et al., 2014; Jung et al., 2015). This evidence concerns the gene HPX and sickle cell disease.