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Astrocytes are highly diversified in structure and function; they control brain homeostasis, support synaptic connectivity, and enable information processing in neural networks. Evolutionary diversification of astrocytes, initially emerging as supportive cells of primitive sensory organs, drove a continuous expansion of astroglial complexity and functional versatility, ultimately making them indispensable neuroprotectors and homeostatic regulators. The large, morphologically elaborate astrocytes of the human brain arguably reflect an evolutionary response to increased neuronal homeostatic demands. Astrocytes are indispensable for synaptic function, serving as the principal regulators of neurotransmitter turnover and neuronal excitability. Astrocytes also govern brain energy metabolism, mitochondrial dynamics, and calcium signaling, thereby actively shaping cortical plasticity and circuits. Astrocytes are fundamental elements of the pathophysiology of neurological, neuropsychiatric, and neurodegenerative diseases, including Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Rett syndrome, genetic astrocytopathies, and neurotrauma, where they demonstrate complex reactive changes directed at tissue preservation and regeneration, but which can also contribute to disease progression. Advances in single\u2010cell transcriptomics, calcium imaging, chemogenetics, and iPSC\u2010based models have transformed our understanding of astrocyte diversity and disease\u2010specific dysfunction, opening new avenues of investigation. Given that no CNS disorder is known to occur without astrocyte involvement, multiple astrocyte\u2010specific molecules represent compelling targets for cell\u2010directed therapeutic strategies.<\/jats:p>","DOI":"10.1111\/apha.70289","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:07:29Z","timestamp":1786939649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Written in the Stars: Astrocyte Biology From Evolution to Disease"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-1171","authenticated-orcid":false,"given":"Carmen","family":"Falcone","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Towson University  Towson Maryland 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