These cascades include defects in transcription, processing, turnover and axonal transport of multiple additional coding and non-coding RNAs, impairments of the DNA damage response, toxic effects of cytoplasmic TDP-43 on mitochondria, and the sequestration of proteins and RNAs into TDP-43 aggregates.5 Therefore, gaps in our knowledge of spatiotemporal events in TDP-43 proteinopathies currently prevent estimating benefits of rescuing STMN2 expression for human patients. This evidence concerns the gene STMN2 and proteostasis deficiencies.