Abstract: Neurodegenerative diseases that affect the motor neurons, including amyotrophic lateral sclerosis (ALS), have little treatment options and are generally rapidly fatal (1, 2). We harnessed the power of unbiased, whole transcriptome differential gene expression analysis, utilizing primary patient cells and tissues to discover genes whose expression defines ALS using published and public data (3, 4). We found significant differential expression of ZFP36L2, encoding ZFP36 ring finger protein-like 2, in the motor neurons of patients with ALS. ZFP36L2 was also differentially expressed in the induced pluripotent stem cell (iPSC)-derived motor neurons of patients with ALS. ZFP36L2 transcript was present at significantly higher levels in ALS patient motor neurons as compared to control motor neurons. These analyses will begin to define the transcriptional landscape of ALS.