Fig. 1

Schematic summarising how cryptic exons (CEs) arise in the context of TDP-43 mislocalisation from the nucleus to the cytoplasm (owing to de-repression of splicing in intronic regions), possible downstream consequences (loss of functional protein, nonsense-mediated decay (NMD) of the cryptic-containing transcript, or translation of a novel cryptic peptide), and opportunities that CEs provide for better understanding disease mechanisms (STMN2, UNC13A, other genes yet to be explored), biomarker development (RNA and protein biomarkers), and therapeutics (via restoration of protein levels, or splicing modification)