Iron accumulation in the brain is a common feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron's involvement spans across proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. The role of iron in disease pathogenesis is complex, with evidence suggesting it may be both a driver and a consequence of protein pathology. Iron is essential for brain function but must be tightly regulated to prevent toxicity. Recent studies highlight the dynamic interplay between iron dysregulation and proteinopathies in neurodegenerative diseases. In AD, iron dysregulation is associated with cognitive decline and is linked to both Aβ and tau pathologies. Iron accumulation may be a consequence of protein pathology or may promote it. Iron is involved in the regulation of APP and tau, influencing their aggregation and toxicity. In PSP, iron accumulation is closely associated with tau pathology, with iron deposition in subcortical regions and the oculomotor nerve. In PD, iron accumulation is linked to motor symptoms and cognitive impairment, with iron levels in the SN and striatum correlating with disease severity. Iron dysregulation in PD may also contribute to the progression of α-synuclein pathology. The role of iron in neurodegenerative diseases is multifaceted, with evidence suggesting it may be a driver or a consequence of protein pathology. Iron dysregulation is associated with the progression of Aβ, tau, and α-synuclein pathologies, and its accumulation may contribute to neurotoxicity through reactive oxygen species and iron homeostatic changes. Understanding the complex relationship between iron and proteinopathies is crucial for developing targeted therapies. Current research highlights the need for further investigation into the mechanisms underlying iron dysregulation in neurodegenerative diseases.Iron accumulation in the brain is a common feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron's involvement spans across proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. The role of iron in disease pathogenesis is complex, with evidence suggesting it may be both a driver and a consequence of protein pathology. Iron is essential for brain function but must be tightly regulated to prevent toxicity. Recent studies highlight the dynamic interplay between iron dysregulation and proteinopathies in neurodegenerative diseases. In AD, iron dysregulation is associated with cognitive decline and is linked to both Aβ and tau pathologies. Iron accumulation may be a consequence of protein pathology or may promote it. Iron is involved in the regulation of APP and tau, influencing their aggregation and toxicity. In PSP, iron accumulation is closely associated with tau pathology, with iron deposition in subcortical regions and the oculomotor nerve. In PD, iron accumulation is linked to motor symptoms and cognitive impairment, with iron levels in the SN and striatum correlating with disease severity. Iron dysregulation in PD may also contribute to the progression of α-synuclein pathology. The role of iron in neurodegenerative diseases is multifaceted, with evidence suggesting it may be a driver or a consequence of protein pathology. Iron dysregulation is associated with the progression of Aβ, tau, and α-synuclein pathologies, and its accumulation may contribute to neurotoxicity through reactive oxygen species and iron homeostatic changes. Understanding the complex relationship between iron and proteinopathies is crucial for developing targeted therapies. Current research highlights the need for further investigation into the mechanisms underlying iron dysregulation in neurodegenerative diseases.