Glucose–6–Phosphate Dehydrogenase (G6PD) is the rate limiting enzyme of the pentose phosphate pathway (PPP), that protects human cells from oxidative stress. There are few reports that suggest that G6PD activity is not stable but varies, possibly due to external factors, though this topic is sparsely explored to date. In addition, there is a strong overlap between areas that were or still are malaria endemic and areas with high prevalence of G6PD deficiency possibly due to a protective effect of G6PD deficiency against malaria. This study aim to identify the factors that regulating G6PD activity in human red blood cells, and what impact does that have on the protective effect of G6PDd against malaria.