While cultures of astrocytes harbouring bi-allelic pathogenic variants in POLG are useful for providing a mechanistic insight to primary impairment of astrocytic functions in response to mitochondrial dysfunction [66, 67], it is crucial POLG-astrocytes are co-cultured with relevant populations of neurons to better understand the relationship between astrocytic and neuronal dysfunction in Alpers’ syndrome, and to fully recapitulate the pathophysiology of POLG-related epilepsy. Here, POLG is linked to Alpers syndrome.