HNRNPU (heterogeneous nuclear ribonucleoprotein U) is a multifunctional RNA-binding protein that plays critical roles in neurodevelopment and cellular regulation. The protein functions as a splicing factor that controls alternative splicing of key transcription factors, including TEAD1, where HNRNPU inhibition leads to exclusion of inhibitory exons and increased TEAD1 activity 1. HNRNPU also regulates NF-κB signaling through direct interaction with FOXN3, competing with IκBα binding and modulating inflammatory responses 2. Loss-of-function mutations in HNRNPU are strongly associated with neurodevelopmental disorders, particularly developmental and epileptic encephalopathy 34. De novo HNRNPU mutations contribute significantly to autism spectrum disorders and epileptic encephalopathies, with the gene showing enrichment for damaging mutations in affected individuals 56. In cancer, HNRNPU expression correlates with cisplatin resistance in bladder cancer, where its knockout enhances chemosensitivity by affecting DNA damage repair pathways and NF1 regulation 7. The protein demonstrates high expression in radial glial progenitors during cerebral cortical development, supporting its critical role in neurodevelopmental processes 6.