The first compelling observations that (i) heme toxicity can be central to the pathogenesis of a human disease allowing heme toxicity to develop as HPX levels decline (i.e., a HPX deficiency state); and (ii) HPX infusions restore circulating HPX levels, reduced mortality, and thus may be a novel therapeutic approach came from studies using mice models of sepsis (Larsen et al., 2010). The gene discussed is HPX; the disease is hyperinsulinemic hypoglycemia, familial, 4.