Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination.

This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell.

Owing to this unique heme-sensing capacity, it plays a crucial role in shutting off protein synthesis during acute heme-deficient conditions.

Thus plays an essential protective role for RBC survival in anemias of iron deficiency.

Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2.