Costa, Mariana ReisGromicho, MartaPronto Laborinho, Ana CatarinaMiltenberger-Miltenyi, GabrielCarvalho, Mamede2021-10-152021-10-152019J Neurol Sci. 2019 Aug 15;403:117-1180022-510Xhttp://hdl.handle.net/10451/49915© 2019 Elsevier B.V. All rights reserved.Amyotrophic lateral sclerosis (ALS) is usually sporadic, but 20% of European ancestry cases have a family history of ALS or frontotemporal dementia (FTD). More than 30 genes confer a higher risk for ALS, and C9orf72, TARDBP, SOD1 and FUS account for nearly 70% of all familial (fALS) cases. Tank-binding kinase 1 (TBK1) is an established causal gene associated with 1% of fALS and/or FTD. It codes for a multifunctional kinase involved in multiple cellular processes, such as neuroinflammation and autophagy. Both loss-of-function (LoF) and missense mutations are associated with an increased risk for ALS-FTD spectrum and mutations that cause a 50% reduction of TBK1 protein levels are considered pathogenic.engAmyotrophic lateral sclerosisFamilial motor neuron disorderPrimary lateral sclerosis phenotypeTBK1 mutationjournal article10.1016/j.jns.2019.06.0291878-5883