PHLDA3 and amyotrophic lateral sclerosis: ROS is one of the few experimentally proven culprits that may underlie astrocyte-driven motor neuron death in ALS,27,28,30 along with recently identified potential candidates.31 The reduction of ROS levels detected in the PHLDA3 siRNA ACM of ALS astrocytes is one of the plausible protective mechanisms underlying limited SG accumulation.26 However, it is not the case for control astrocytes in which ROS production remained unchanged upon PHLDA3-KD, yet their ACM provided protection against SA-induced neuronal stress.