RNA-binding proteins (RBPs) constitute central regulators of post-transcriptional gene expression and have been increasingly recognized as critical contributors to the pathogenesis of cancer, neurodegenerative disorders, and autoimmune diseases. However, in contrast to well-established drug targets such as kinases and G protein-coupled receptors, RBPs remain largely underexploited owing to their intrinsic structural heterogeneity, dynamic RNA interactions, and paucity of canonical ligand-binding pockets. In this review, we synthesize current knowledge on the roles of RBPs in disease, outline recent advances in the design of small-molecule modulators, and highlight innovative applications of high-throughput screening and chemical biology approaches for target identification and validation. We further discuss emerging concepts and challenges in translating RBP modulators into therapeutics, providing a forward-looking perspective on how these efforts may reshape small-molecule drug discovery in this evolving field.

RNA binding proteins  /  Post-transcriptional gene expression  /  Disease  /  Small-molecule modulators  /  High-throughput screening  /  Chemical biology approaches  /  Target identification  /  Drug discovery