Much of the research into the molecular mechanisms underlying the pathology of FMR1-associated conditions has focused on the neurological aspects: the aim of this review is to critically appraise putative mechanisms underlying the pathogenesis of FXPOI, specifically the evidence investigating the RNA gain-of-function hypothesis and the contribution of repeat-associated non-AUG (RAN) translation, drawing on parallels in FXTAS and advances made in that disease. Here, FMR1 is linked to fragile X-associated tremor/ataxia syndrome.