Amyotrophic Lateral Sclerosis (ALS) is a fatal and incurable neurological disorder characterized by the prion-like aggregation of TAR DNA-binding protein 43 (TDP-43). TDP-43 is also implicated in other neurodegenerative conditions, such as frontotemporal dementia (FTD) and Alzheimer's disease, making it a promising candidate for clinical intervention. Challengingly, only a small proportion of neurons exhibit TDP-43 pathology, and thus broad administration of therapeutics could drive significant off-target toxicity. Loss of TDP-43 function during ALS pathophysiology leads to expression of CEs, introducing premature termination codons into transcripts and hindering production of essential neurological proteins. We questioned whether this cryptic splicing mechanism could be exploited to control protein expression.