Abnormal regulation of the actin cytoskeleton results in several pathological conditions affecting primarily the nervous system. Those of genetic origin arise during development, but others manifest later in life. Actin regulation is also affected profoundly by environmental factors that can have sustained consequences for the nervous system. Those consequences follow from the fact that the actin cytoskeleton is essential for a multitude of cell biological functions ranging from neuronal migration in cortical development and dendritic spine formation to NMDA receptor activity in learning and alcoholism. Improper regulation of actin, causing aggregation, can contribute to the neurodegeneration of amyloidopathies, such as Down's syndrome and Alzheimer's disease. Much progress has been made in understanding the molecular basis of these diseases.