MTF1 (metal regulatory transcription factor 1) is a zinc-dependent transcriptional regulator that functions as a master controller of cellular heavy metal homeostasis 1. MTF1 binds to metal-responsive elements (MREs) in gene promoters and activates transcription of metallothionein genes and other heavy metal response genes in response to intracellular zinc accumulation 2. The Hippo pathway kinase LATS phosphorylates and inhibits MTF1 to attenuate heavy metal responses, while accumulated zinc directly binds LATS to inhibit its activity, creating a regulatory feedback loop 3. Beyond metal homeostasis, MTF1 has emerged as a critical neuroprotective factor. Genome-wide screening identified MTF1 as a suppressor of mutant huntingtin toxicity in Huntington's disease; forced MTF1 expression counteracts oxidative stress and cell death in both cellular and animal models, reducing motor defects and protein aggregates in R6/2 mice 4. In cancer, MTF1 expression correlates with disease prognosis in context-dependent ways: high MTF1 associates with poor outcomes in hepatocellular carcinoma and brain glioma but favorable prognosis in kidney, lung, ovarian, and breast cancers 5. Mechanistically, MTF1 knockdown increases reactive oxygen species and promotes cell death in hepatocellular carcinoma cells 5. MTF1 also participates in cuproptosis pathways and has been identified as a hub gene in periodontitis pathogenesis 6, 7.