Protein misfolding and accumulation are prevalent in many neurodegenerative disorders, leading to the formation of toxic intra- and extracellular aggregates. While microglia play a predominant role in removing extracellular aggregated proteins, astrocytes also contribute to this process. However, the molecular mechanisms by which astrocytes clear misfolded proteins remain largely unknown. This article provides an overview of the transition from soluble monomers to insoluble fibrils in amyloid proteins, focusing on α-Synuclein and Tau as archetypal examples. It highlights the mechanisms underlying astrocyte-mediated clearance, including their ability to recognize, collect, internalize, and digest extracellular protein aggregates. The potential of targeting astrocyte-mediated clearance as a therapeutic approach for neurodegenerative disorders characterized by protein misfolding and accumulation is explored. The article discusses the origins of α-Syn and Tau in astrocytes, the transfer of protein aggregates from neurons to astrocytes, and the phagocytic processes involved in astrocyte-mediated clearance. It also examines the elimination of protein aggregates by astrocytes and the potential impact of astrocyte dysfunction on neuronal function. Finally, the article considers the therapeutic potential of targeting glial cells to block proteinopathies.Protein misfolding and accumulation are prevalent in many neurodegenerative disorders, leading to the formation of toxic intra- and extracellular aggregates. While microglia play a predominant role in removing extracellular aggregated proteins, astrocytes also contribute to this process. However, the molecular mechanisms by which astrocytes clear misfolded proteins remain largely unknown. This article provides an overview of the transition from soluble monomers to insoluble fibrils in amyloid proteins, focusing on α-Synuclein and Tau as archetypal examples. It highlights the mechanisms underlying astrocyte-mediated clearance, including their ability to recognize, collect, internalize, and digest extracellular protein aggregates. The potential of targeting astrocyte-mediated clearance as a therapeutic approach for neurodegenerative disorders characterized by protein misfolding and accumulation is explored. The article discusses the origins of α-Syn and Tau in astrocytes, the transfer of protein aggregates from neurons to astrocytes, and the phagocytic processes involved in astrocyte-mediated clearance. It also examines the elimination of protein aggregates by astrocytes and the potential impact of astrocyte dysfunction on neuronal function. Finally, the article considers the therapeutic potential of targeting glial cells to block proteinopathies.