Of interest, a novel diagnostic protein biomarker is derived from the cryptic exon-containing hepatoma-derived growth factor-like protein 2 (HDGFL2), whose content in the CSF is strictly dependent on TDP-43 loss of splicing activity in ALS and FTD and is significantly increased in sporadic ALS patients as well as in presymptomatic and symptomatic C9ORF72 mutation carriers [83]. The gene discussed is TARDBP; the disease is frontotemporal dementia.