Ferritin: The Body's Iron Storage Protein — Structure, Function, and Clinical Significance

Ferritin is a ubiquitous intracellular protein that stores iron in a soluble, non-toxic, bioavailable form. It is the primary marker of total body iron stores.

Structure

• 24 subunits (H-heavy and L-light chains) form a hollow nanocage (~12 nm diameter).
• Each shell holds up to 4,500 Fe³⁺ atoms as ferrihydrite mineral core.
• H-subunits: ferroxidase activity (Fe²⁺ → Fe³⁺); L-subunits: nucleation, long-term storage.

Physiological Roles

• Iron homeostasis: buffers against deficiency and overload.
• Provides iron for hemoglobin, myoglobin, cytochromes, DNA synthesis.
• Sequesters iron from pathogens (nutritional immunity).
• Serum ferritin correlates with stored iron (1 ng/mL ≈ 8–10 mg storage iron).

Clinical Interpretation

• Low ferritin (<15–30 ng/mL): Iron deficiency (most sensitive early marker).
• High ferritin: Iron overload (hemochromatosis, transfusions), inflammation (acute phase reactant), liver disease, malignancy, metabolic syndrome. CRP helps distinguish.

Regulation

Iron-responsive elements (IREs) on ferritin mRNA: high iron → IRP dissociation → translation ↑. Transcriptional control by inflammatory cytokines (IL-1, TNF-α).

Ferritin is both a storage depot and a dynamic biomarker — interpret in clinical context.