Thus, RNA neurotoxicity via R-loops and SAM68, protein aggregation and unbalanced excitability have been proposed to underlie the ataxia and cerebellar atrophy in A-T, in view of similar clinico-pathological findings in other monogenic spinocerebellar ataxias where mutant AOA2, FRDA, ATXN2, ITPR1 trigger similar cytosolic pathways in pathogenesis [17,55,56,57]. Here, ITPR1 is linked to Ataxia.