TARDBP and amyotrophic lateral sclerosis: Indeed, cryptic exons generated by mis-splicing due to TDP-43 loss of function are not only able to inhibit the expression of mRNA transcript through promoting their degradation, but have been shown to induce the translation of de novo proteins from pathological transcripts.81 Since TDP-43 depletion in vitro resembles splicing abnormalities observed in ALS/FTD brains, these findings may offer a promising approach for assessing TDP-43 activity in patient CSF and point towards novel mechanisms underlying ALS/FTD pathophysiology.