The pathologic hallmark of Parkinson's disease is the accumulation of α-synuclein-containing Lewy bodies/neurites almost exclusively in neurons, and rarely in glial cells. However, emerging evidence suggests that glia such as astrocytes play an important role in the development of α-synuclein pathology. Using induced pluripotent stem-derived dopaminergic neurons and astrocytes from healthy subjects and patients carrying mutations in lysosomal ATP13A2 , a monogenic form of synucleinopathy, we found that astrocytes rapidly internalized α-synuclein, and exhibited higher lysosomal degradation rates compared with neurons. Moreover, coculturing astrocytes and neurons led to decreased accumulation of α-synuclein in neurons and consequently diminished interneuronal transfer of α-synuclein. These protective functions of astrocytes were attenuated by ATP13A2 deficiency, suggesting that the loss of ATP13A2 function in astrocytes at least partially contributes to neuronal α-synuclein pathology. Together, our results h...