RNA-binding proteins in tumor lipid metabolic reprogramming: from mechanistic understanding to targeted therapy

Dysregulation of lipid metabolism is a central hallmark of tumor cells, providing not only the energy reserves necessary for rapid proliferation but also the structural precursors required for membrane biosynthesis. RNA-binding proteins (RBPs), as central executors of post-transcriptional regulation, play an increasingly recognized role in tumor lipid metabolic reprogramming. Studies have shown that RBPs systematically regulate the mRNA stability, translation efficiency, and subcellular localization of genes related to lipid metabolism by selectively recognizing and binding to specific target RNAs, thereby coordinating lipid synthesis, lipolysis, transport, and storage to ultimately drive the remodeling of tumor metabolic networks. Although the link between RBPs and lipid metabolism has attracted growing attention, this review is organized specifically around an overview of RBPs and the perspective of RBP-targeted therapies. Adopting the classification of classical and non-classical RBPs as a unifying framework, this article systematically reviews the molecular regulatory mechanisms by which RBPs mediate lipid metabolic reprogramming in the context of lipid synthesis, degradation, transport, and storage, as well as their contributions to tumor initiation, progression, immune evasion, and microenvironment adaption, with particular attention to the functional heterogeneity of RBP-RNA regulatory axes across tumor types. Beyond mechanistic understanding, the article evaluates therapeutic strategies targeting RBPs, including molecular glues, PROTACs, and RNA-based interventions, together with their key challenges, such as drug developability, delivery specificity, and resistance mechanisms, aiming to provide a theoretical framework and cutting-edge perspectives for elucidating tumor metabolic plasticity and advancing RBP-based precision therapy.