must be carefully monitored in terms of establishing the validity of the resulting model. Examining the behaviour of the model by simulating it at different values of initial conditions or other parameters (parameter scans) is important to establish the limits of utility of the model. Global sensitivity analysis is another approach that determines the boundaries of parameter variation that the model tolerates before it becomes too distant from the actual system behaviour. Model validation is an essential step in modelling. Validation should be carried out by enquiring if the model is able to match experimental observations that were not used to calibrate it. Here the model was validated by the simulation of haemochromatosis disease, where the model behaviour matched the clinical data (Table \[table:tableHFEKO\]).

The precise regulatory mechanism behind transferrin receptors and HFE controlling hepcidin expression remains to be validated experimentally, however the model presented here supports current understanding that the interaction of TfR2 and HFE form the signal transduction pathway that leads to the induction of hepcidin expression [@Gao2009Interaction].

The global metabolic control analysis results support the identification of the transferrin receptors, particularly TfR2, and HFE as potential therapeutic targets; a result that is robust even to inaccuracies in 