MT2A (metallothionein 2A) is a cysteine-rich metal-binding protein primarily involved in heavy metal homeostasis and cellular stress responses. The protein functions as a chelator of toxic metal ions, particularly copper and zinc, maintaining intracellular metal ion balance and protecting cells from metal-induced toxicity 12. MT2A expression is transcriptionally regulated by heavy metals and glucocorticoids, with the protein localizing to both cytoplasm and nucleus 1. Mechanistically, MT2A regulates copper homeostasis and prevents cuproptosis (copper-dependent cell death) by reducing intracellular Cu²⁺ levels and maintaining mitochondrial function 12. The protein contains critical functional sites, including Lys-31, essential for its neuroprotective effects 1. Clinically, MT2A dysregulation is associated with multiple pathologies. Elevated MT2A expression marks pathogenic macrophage populations in rheumatoid arthritis synovium, enriched before disease onset 3. MT2A is upregulated during skin wound reepithelialization 4 and serves as a predictive biomarker for intervertebral disc degeneration 5. In neurodegeneration, MT2A upregulation mediates neuroprotection in Parkinson's disease through astrocyte-mediated copper regulation 1. In osteosarcoma, MT2A glycosylation status influences cell survival and chemotherapy response 6. These findings establish MT2A as a critical regulator of metal homeostasis with broad therapeutic relevance.