On the basis of our findings we formulate the following model (Fig. 5): the malaria-protective trait of sickle cell haemoglobin, HbC and HbF results from a cascade of events that begins with the instability of these haemoglobin variants and a tendency to increased spontaneous auto-oxidation, which in turn leads to elevated quantities of irreversibly oxidized haemichromes, ferryl haemoglobin, protein radicals, free ferryl haem and other oxidants (Table 1)3, 24, 26, 27, 29. Here, KRT88P is linked to malaria.