Our recent study reported a significant increase of a recently identified stress response element, pleckstrin homology-like domain family A—member 3 (PHLDA3), in human superoxide dismutase 1 (SOD1D90A)-mutant ALS astrocytes.7 It remains unclear whether astrocytic expression of PHLDA3 plays a detrimental or an adaptive protective role, as its function varies in different tissue types. This evidence concerns the gene PHLDA3 and amyotrophic lateral sclerosis.