Ultimately, this work has implications for the study of PEG10, and mRNA splicing in neurological diseases associated with elevated PEG10 abundance.<h4>Highlights</h4>PEG10 NC expression influences abundance of transcripts implicated in ALS PEG10 NC expression leads to an exon skipping event in <i>neuregulin 3 (NRG3)</i> NRG3 expression is decreased along dendrites of PEG10 NC expressing human neuronsExpression of PEG10 NC mimics changes observed in human ALS. Here, NRG3 is linked to amyotrophic lateral sclerosis.