Here, in the present study, we aimed to extend these previous findings by systematically evaluating (1) ALS reactive astrocyte molecular and functional features across different mutations and models, and (2) the degree to which ALS astrocytes resemble deleterious inflammatory astrocytes (induced by treatment of the healthy state with TNF, IL1A, and C1q) or neuroprotective astrocytes (induced by middle cerebral artery occlusion [MCAO] and spinal cord injury [SCI] models). Here, TNF is linked to amyotrophic lateral sclerosis.