SLC39A8 (also known as ZIP8) is a member of the solute carrier family 39 that functions as a zinc and iron transporter. Genetic variants in SLC39A8 have been associated with Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions.
<div class="infobox infobox-gene"> <table> <tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Solute Carrier Family 39 Member 8</th></tr> <tr><td><strong>Gene Symbol</strong></td><td>SLC39A8</td></tr> <tr><td><strong>Full Name</strong></td><td>Solute Carrier Family 39 Member 8</td></tr> <tr><td><strong>Chromosome</strong></td><td>4q24</td></tr> <tr><td><strong>NCBI Gene ID</strong></td><td>[64116](https://www.ncbi.nlm.nih.gov/gene/64116)</td></tr> <tr><td><strong>OMIM</strong></td><td>608732</td></tr> <tr><td><strong>Ensembl ID</strong></td><td>ENSG00000138821</td></tr> <tr><td><strong>UniProt ID</strong></td><td>[Q9C0K1](https://www.uniprot.org/uniprot/Q9C0K1)</td></tr> <tr><td><strong>Associated Diseases</strong></td><td>[Parkinson's Disease](/diseases/parkinsons-disease), [Alzheimer's Disease](/diseases/alzheimers-disease), Leigh Syndrome, Congenital Disorder of Glycosylation</td></tr> </table> </div>
Overview
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SLC39A8 — Solute Carrier Family 39 Member 8
SLC39A8 (also known as ZIP8) is a member of the solute carrier family 39 that functions as a zinc and iron transporter. Genetic variants in SLC39A8 have been associated with Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions.
<div class="infobox infobox-gene"> <table> <tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Solute Carrier Family 39 Member 8</th></tr> <tr><td><strong>Gene Symbol</strong></td><td>SLC39A8</td></tr> <tr><td><strong>Full Name</strong></td><td>Solute Carrier Family 39 Member 8</td></tr> <tr><td><strong>Chromosome</strong></td><td>4q24</td></tr> <tr><td><strong>NCBI Gene ID</strong></td><td>[64116](https://www.ncbi.nlm.nih.gov/gene/64116)</td></tr> <tr><td><strong>OMIM</strong></td><td>608732</td></tr> <tr><td><strong>Ensembl ID</strong></td><td>ENSG00000138821</td></tr> <tr><td><strong>UniProt ID</strong></td><td>[Q9C0K1](https://www.uniprot.org/uniprot/Q9C0K1)</td></tr> <tr><td><strong>Associated Diseases</strong></td><td>[Parkinson's Disease](/diseases/parkinsons-disease), [Alzheimer's Disease](/diseases/alzheimers-disease), Leigh Syndrome, Congenital Disorder of Glycosylation</td></tr> </table> </div>
Overview
Mermaid diagram (expand to render)
SLC39A8 is a human gene whose product sLC39A8 encodes the zinc and iron transporter protein ZIP8 (also called Zrt- and Irt-like protein 8). This protein plays a critical role in metal homeostasis by facilitating the uptake of zinc and iron across cellular membranes, including the [blood-brain barrier](/entities/blood-brain-barrier). Variants in SLC39A8 have been implicated in Parkinson's Disease, Alzheimer's Disease, Other Conditions. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
SLC39A8 encodes the zinc and iron transporter protein ZIP8 (also called Zrt- and Irt-like protein 8). This protein plays a critical role in metal homeostasis by facilitating the uptake of zinc and iron across cellular membranes, including the blood-brain barrier.
Key functions include:
Zinc transport: ZIP8 mediates cellular zinc uptake, essential for enzyme function, protein structure, and signaling pathways[@liu2023]
Iron homeostasis: The transporter also imports iron, crucial for mitochondrial function and neurotransmitter synthesis[@wang2022]
Blood-brain barrier permeation: SLC39A8 expression on endothelial cells of the BBB allows metal entry into the brain[@gomes2021]
Expression Pattern
SLC39A8 shows broad expression across multiple tissues with highest levels in:
Kidney (proximal tubules)
Liver (hepatocytes)
Brain (especially in [neurons](/entities/neurons) and glial cells)
Small intestine
In the brain, ZIP8 is expressed in dopaminergic neurons of the substantia nigra, making it particularly relevant to Parkinson's disease pathogenesis.
Disease Associations
Parkinson's Disease
Genome-wide association studies (GWAS) have identified SLC39A8 variants as a risk factor for Parkinson's disease[@nalls2019]. These variants may lead to:
Altered zinc homeostasis in dopaminergic neurons
Increased susceptibility to oxidative stress
Impaired mitochondrial function
Alzheimer's Disease
SLC39A8 variants have been linked to Alzheimer's disease risk, potentially affecting:
[Amyloid-beta](/proteins/amyloid-beta) metal ion interactions
[Tau](/proteins/tau) phosphorylation regulation
Neuroinflammation modulation
Other Conditions
| Condition | Variant Type | Mechanism | |-----------|--------------|-----------| | Leigh Syndrome | Severe loss-of-function | Mitochondrial dysfunction | | Congenital Disorder of Glycosylation Type II | Hypomorphic variants | Glycosylation defects |
Therapeutic Implications
Targeting SLC39A8 represents a potential therapeutic strategy for neurodegenerative diseases:
Zinc modulation: Small molecules that modulate ZIP8 activity could restore zinc homeostasis
Gene therapy: AAV-based delivery of wild-type SLC39A8 to restore function
Metal chelation: Strategic chelation approaches targeting ZIP8-mediated uptake
See Also
[Metal Metabolism](/mechanisms/metal-metabolism)
[Iron Homeostasis](/mechanisms/iron-homeostasis)
[Zinc Signaling in Brain](/mechanisms/zinc-signaling)