The sequestration of Sam68 into intranuclear RBP aggregates was shown to be an early disease event and crucial in fragile-X-tremor-ataxia-syndrome (FXTAS), impacting the mRNA splicing/metabolism in dendrites and thus determining the number of glutamatergic synapses [81,82]. The gene discussed is KHDRBS1; the disease is fragile X-associated tremor/ataxia syndrome.