Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative diseases characterized by the nuclear clearance and cytoplasmic aggregation of transactive response DNA/RNA-binding protein of 43 kDa (TDP43). Alternative splicing of TARDBP, the gene encoding TDP43, leads to a surprising diversity of RNA and protein isoforms with unique functions and potential implications for disease pathogenesis. Here, we review the production, properties, and functional co