IRF3 and amyotrophic lateral sclerosis: As discussed above, GWAS studies have reported an excess of rare loss-of-function variants in the TBK1-related innate immunity pathway in FTD-TDP patients compared to controls [46] and TBK1 mutations observed in ALS and FTD-TDP patients have previously been shown to reduce the activation of one of the most well-characterised transcription factors involved in innate immunity, interferon regulatory factor 3 (IRF3) [55].