Abstract: Zinc homeostasis genes are a general term for a family of genes responsible for regulating the concentration of intracellular and extracellular zinc ions, including the SLC39 (ZIP) family, the SLC30 (ZnT) family, and the metallothionein family. As an essential trace element, zinc is involved in biomolecular synthesis, energy metabolism, redox regulation, and gene expression. Recent studies have shown that abnormal expression of zinc homeostasis genes mediates neuronal apoptosis through multiple pathways, including oxidative stress and neuroinflammation. Imbalance in zinc homeostasis can result in the pathological development of various neurodegenerative disorders, including the deposition of amyloid-β in Alzheimer’s disease and the aberrant aggregation of α-synuclein in Parkinson’s disease. Therefore, regulating the expression of zinc homeostasis genes to restore normal zinc levels in vivo may be an effective strategy for treating neurodegenerative diseases. This review comprehensively summarizes the current status of research exploring zinc homeostasis genes across various family subtypes, as well as the altered expression of these genes in different neurodegenerative diseases and the underlying mechanisms. Finally, we propose zinc chelator supplementation as a novel interventional therapy for neurodegenerative diseases. This proposal includes an evaluation of the feasibility, safety, and limitations of this treatment, providing an innovative perspective for the clinical management of neurodegenerative diseases in the future. 

Key words: Alzheimer’s disease, neuroinflammation, neuronal cell death, oxidative stress, Parkinson’s disease, Schizophrenia, synaptic dysfunction, zinc chelators, zinc homeostasis genes, zinc signaling pathways