Proposed pathogenic mechanisms for microsatellite repeat diseases. Microsatellite expansions (red triangles) in noncoding (UTRs, small blue boxes; introns, black lines) regions may result in RNA (yellow boxes) gain-of-function (RNA GOF), protein (grey and colored circles) loss-of-function (protein LOF) or repeat-associated non-ATG (RAN) protein GOF (RAN GOF). In conventional coding regions (open reading frame, ORF), expansions might cause a protein GOF effect such as the CAG expansion in SCA3 which results in a polyGln (polyQ, brown circles) expansion that either accumulates in cellular inclusions or alters mutant ATXN3 (mATXN3) interactions. Note that RAN translation of the C9ORF72 GGGGCCexp repeat in ALS/FTD produces polyGlyAla (GA), polyGlyPro (GP) and polyGlyArg (GR) dipeptide repeat proteins due to the recognition an RNS secondary structure (red hairpin) by the ribosome (orange ellipsoids).