Iron is essential for brain development and function, and its abnormal distribution and concentration in brain tissue are associated with neurodegenerative diseases. The alteration of brain iron homeostasis is a common feature of many neurodegenerative conditions, but whether iron is the primary actor or a consequence of degeneration remains unclear. Both iron overload and deficiency have profound effects on cellular functioning and contribute to neuronal death through mechanisms such as oxidative damage, membrane integrity loss, proteostasis disruption, and mitochondrial dysfunction. This review aims to elucidate the consequences of iron dyshomeostasis on brain health by summarizing the molecular mechanisms linking iron and neuronal death. Iron metabolism in the brain is regulated by the blood-brain barrier (BBB), with specific regions expressing different levels of transferrin receptor (TfR)1, which controls iron absorption. Astrocytes play a crucial role in regulating iron transport through hepcidin production. Aging and neuroinflammation can lead to increased brain iron, contributing to neurodegeneration. Excess iron can trigger ferroptosis, a form of iron-dependent cell death, and impair proteasomal and lysosomal systems. Iron deficiency can also lead to cognitive and psychomotor impairments. The relationship between iron and psychiatric disorders, such as schizophrenia and depression, is also discussed. Understanding the complex interplay between iron and neurodegeneration is crucial for developing effective therapies.Iron is essential for brain development and function, and its abnormal distribution and concentration in brain tissue are associated with neurodegenerative diseases. The alteration of brain iron homeostasis is a common feature of many neurodegenerative conditions, but whether iron is the primary actor or a consequence of degeneration remains unclear. Both iron overload and deficiency have profound effects on cellular functioning and contribute to neuronal death through mechanisms such as oxidative damage, membrane integrity loss, proteostasis disruption, and mitochondrial dysfunction. This review aims to elucidate the consequences of iron dyshomeostasis on brain health by summarizing the molecular mechanisms linking iron and neuronal death. Iron metabolism in the brain is regulated by the blood-brain barrier (BBB), with specific regions expressing different levels of transferrin receptor (TfR)1, which controls iron absorption. Astrocytes play a crucial role in regulating iron transport through hepcidin production. Aging and neuroinflammation can lead to increased brain iron, contributing to neurodegeneration. Excess iron can trigger ferroptosis, a form of iron-dependent cell death, and impair proteasomal and lysosomal systems. Iron deficiency can also lead to cognitive and psychomotor impairments. The relationship between iron and psychiatric disorders, such as schizophrenia and depression, is also discussed. Understanding the complex interplay between iron and neurodegeneration is crucial for developing effective therapies.