The molecular mechanism underlying FXPOI is enigmatic, and while the study of FXTAS and other expanded-repeat disorders has provided some insight, the discovery of RAN translation adds an additional complexity as to whether CGG-repeats in the 5′UTR of FMR1 elicit toxicity via RNA gain-of-function or protein-based means, or a combination of both. Here, FMR1 is linked to fragile X-associated tremor/ataxia syndrome.