HNRNPUL1 is an RNA-binding protein that functions as a transcriptional regulator with pleiotropic roles across development and disease. Mechanistically, HNRNPUL1 controls transcription and alternative splicing through direct binding to RNA and interactions with spliceosomal proteins 1. In developmental contexts, zebrafish studies demonstrate that Hnrnpul1 regulates genes involved in translation, ubiquitination, and DNA damage, with loss-of-function resulting in skeletal defects, limb malformations, and craniofacial abnormalities 1. A homozygous frameshift variant in HNRNPUL1 was identified in human siblings with congenital limb malformations, suggesting evolutionary conservation of its developmental role 1. In hematologic malignancies, HNRNPUL1 serves as a fusion partner for MEF2D in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), representing a high-risk subtype comprising 5.3% of cases lacking recurring alterations 2. MEF2D-HNRNPUL1 fusion results in enhanced transcriptional activity and HDAC9 activation, with sensitivity to histone deacetylase and PI3K inhibitors 23. The MEF2D-HNRNPUL1 fusion exhibits distinct immunophenotypes and poor clinical outcomes 23. Beyond leukemia, HNRNPUL1 regulates chemotherapy resistance in esophageal squamous cell carcinoma by controlling circular RNA MAN1A2 formation, associating with recurrence in cisplatin-treated patients 4. In cervical and lung cancers, HNRNPUL1 expression is post-transcriptionally regulated through ac4C modification and O-glycosylation, driving cancer progression 56.