The human cell culture platform allowed us to explore whether PHLDA3 expression-related changes in ALS spinal astrocytes could directly affect non-cell autonomous pathogenesis relevant to astrocyte–neuron interactions in ALS.1 ALS astrocytes with a greater PHLDA3 content triggered a neuronal stress response indicated by SG accumulation22,26 or potentiated this when induced by SA, while control astrocytes had only a limited effect. Here, PHLDA3 is linked to amyotrophic lateral sclerosis.