Hepcidin is initially synthesized as an 84-amino acid preprohormone (preprohepcidin) which undergoes sequential cleavages to form the active, mature hormone.

Only the 9 N-terminal amino acids are essential for hepcidin's biological activity, specifically its ability to bind to ferroportin and regulate iron metabolism.

This suggests that hepcidin is able to regulate iron export independently of ferroportin endocytosis and ubiquitination, and is thus quickly inducible and reversible.

[20] Inflammation causes an increase in hepcidin production by releasing the signaling molecule interleukin-6 (IL-6), which binds to a receptor and upregulates the HAMP gene via the JAK/STAT pathway.

[21] Erythroferrone, produced in red blood cells (erythroblasts), has been identified as inhibiting hepcidin, thus providing more iron for hemoglobin synthesis in situations such as stress erythropoiesis.

[22][23] Vitamin D has been shown to decrease hepcidin, both in cell models looking at transcription and when given in large doses to human volunteers.

[24] Hepcidin was initially reported and named in January 1998,[18] after it was observed that it was produced in the liver and appeared to have bactericidal (bacteria-killing) properties.

[29] Soon after this discovery, researchers discovered that hepcidin production in mice increases in conditions of iron overload as well as inflammation.

Studies have found that measuring hepcidin would help establish the optimal treatment for a patient,[30] but as this is not widely available, C-reactive protein (CRP) is used as a surrogate marker.

[31] Beta thalassemia, one of the most common congenital anemias, arises from partial or complete failure to synthesize beta-globin, a component of hemoglobin.

The serial analyses of beta thalassemic mice indicate that hemoglobin levels decrease over time, while the concentration of iron in the liver, spleen, and kidneys increases significantly.

Increasing expression of hepcidin in beta thalassemic mice limits iron overload, and also decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia.