ARGLU1 in Glioma: A Novel Potential Regulator of Splicing, DNA Repair, and Therapeutic Resistance

ARGLU1 (Arginine and Glutamate Rich1) is a newly identified nuclear protein with suggested multifunctional roles that may be implicated in the pathogenesis and therapeutic resistance of glioma, the most common primary malignant brain tumor. The high heterogeneity and treatment resistance of gliomas pose central challenges in clinical management. ARGLU1 has been implicated in maintaining genomic stability and may contribute to tumor progression by regulating RNA splicing and DNA damage repair pathways. This review systematically summarizes the structural and functional features of ARGLU1 and discusses its potential molecular mechanisms in glioma. These include its influence on the spliceosome assembly, alternative splicing events, and key DNA repair pathways such as homologous recombination (HR) and Fanconi anemia (FA). Furthermore, it discusses the hypothesis that ARGLU1 may enhance DNA repair capacity and thereby influence glioma resistance to temozolomide (TMZ) and radiotherapy. Targeting ARGLU1 may offer a strategy to overcome this resistance. Finally, the review outlines current research limitations and future directions, aiming to provide a new theoretical foundation for the precision treatment of glioma.