RNArchitects: how hnRNPs shape neuronal landscapes

Neurons rely on finely tuned RNA regulatory mechanisms to sustain their specialized functions, with heterogeneous nuclear ribonucleoproteins (hnRNPs) emerging as key regulators of these processes. hnRNPs exert multilayered control over synaptic plasticity, axonal function, and neurodevelopmental gene expression by dynamically coordinating mRNA splicing, stability, transport and local translation. Given their pivotal role in neuronal RNA metabolism, recent discoveries have highlighted how hnRNP dysfunction drives pathological RNA dysregulation across a spectrum of neurological disorders. This review provides insights into hnRNP-mediated RNA regulation in the brain, examines their contributions to neurological diseases, and explores how targeting these proteins could pave the way for novel therapeutic strategies to preserve neuronal integrity across diverse neurological conditions.