| Gene | [FTL](/genes/ftl) |
| UniProt | [P02792](https://www.uniprot.org/uniprot/P02792) |
| MW | 19-21 kDa (subunit) |
| Location | Cytosol, nucleus, mitochondria |
| PDB | [2FFX](https://www.rcsb.org/structure/2FFX) |
Ferritin light chain (FTL) is one of two subunits that compose ferritin, the primary iron storage protein in cells. Ferritin forms a 24-subunit spherical shell capable of storing up to 4,500 iron atoms in a bioavailable, non-toxic form. FTL lacks ferroxidase activity (unlike ferritin heavy chain, FTH1) but contributes to iron nucleation and storage stability. FTL mutations cause neurodegeneration with brain iron accumulation (NBIA), and ferritin is increasingly recognized as a therapeutic target in Alzheimer's and Parkinson's diseases.
Ferritin is a 24-mer heteropolymer of FTL and FTH1 subunits:
| Feature | FTL | FTH1 |
|---|---|---|
| Ferroxidase activity | No | Yes |
| Iron nucleation | Yes | Yes |
| Tissue ratio | Variable (1:1 to 30:1) | Variable |
| Hemosiderin formation | Higher propensity | Lower |
Ferritin provides safe iron sequestration:
Ferritin maintains cellular iron balance:
FTL translation is regulated by iron:
FTL mutations cause NBIA type 3 (neuroferritinopathy):
Ferritin and iron homeostasis are altered in AD:
Ferritin light chain expression may be differentially regulated compared to heavy chain in AD neurons.
Iron accumulation in substantia nigra involves ferritin:
Ferritin plays a central role in ferroptosis:
Strategies targeting ferritin-associated iron:
| Agent | Mechanism | Status |
|---|---|---|
| Deferiprone | BBB-penetrant chelator | Clinical trials (PD, AD) |
| Deferoxamine | Chelator, may mobilize ferritin iron | Limited by BBB penetration |
| Deferasirox | Oral chelator | Research use |
Preventing ferritin degradation may protect against ferroptosis:
Caused by FTL mutations:
FTL 5' IRE mutations cause:
| Partner | Function | Disease Relevance |
|---|---|---|
| FTH1 | Heteropolymer formation | Iron storage |
| NCOA4 | Ferritinophagy receptor | Ferroptosis |
| IRP1/IRP2 | IRE-binding regulators | Iron homeostasis |
| Aβ peptide | Plaque-associated | AD iron dysregulation |
| α-synuclein | Aggregation-associated | PD iron homeostasis |
Hentze et al. [A conserved iron-responsive element in the 5' untranslated region of ferritin mRNAs](https://doi.org/10.1016/0092-8674(88). Cell. 1988. ↩︎
Curtis et al. Mutation in the gene encoding ferritin light polypeptide in dominant adult-onset basal ganglia disease. Nat Genet. 2001. ↩︎
Connor et al. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res. 1995. ↩︎
Friedman et al. Ferritin particles in the substantia nigra in Parkinson's disease. J Neuropathol Exp Neurol. 1985. ↩︎
Mancias et al. Quantitative proteomics reveals NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 2014. ↩︎