VCP and amyotrophic lateral sclerosis: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia share genetic disruptions (for example, C9orf72, OPTN, VCP, TMEM106B and progranulin (PGRN)) that impair normal Golgi–endolysosomal trafficking, severely reducing intracellular protein handling and degradation capabilities99.