Small molecule binding of RNA repeat expansions releases sequestered RNA-binding proteins (RBPs). (A) Schematic of RBP sequestration by RNA repeat expansions. (i) RBPs, such as splicing factors, are sequestered by RNA repeat expansions, contributing to disease pathology. (ii) Small molecules competitively bind to RNA repeats and release sequestered proteins, resulting in rescue of splicing defects, reduction in RNA foci, and repression of repeat-associated non-ATG (RAN) translation. (B) Schematic of alternative splicing resulting from the presence or absence of endogenous splicing factors. (C) The RNA:protein complexes that contribute to myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), fragile X-associated tremor and ataxia syndrome (FXTAS), and C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS).