HNRNPM (heterogeneous nuclear ribonucleoprotein M) is a multifunctional RNA-binding protein with primary roles in pre-mRNA splicing and transcriptome regulation. As a core splicing factor, hnRNPM binds avidly to poly(G) and poly(U) RNA sequences and participates in alternative splicing decisions through spliceosomal complex assembly 1. Beyond canonical splicing, hnRNPM functions as a guardian of transcriptome integrity by repressing cryptic splicing events at deep intronic regions, particularly at long interspersed nuclear elements (LINEs), preventing the generation of interferon-activating double-stranded RNAs 2. hnRNPM exhibits non-canonical functions independent of its splicing role. SUMOylation at lysine 17 regulates its interaction with glycolytic enzyme PFKFB3, suppressing lactate production and colorectal cancer progression 3. In cancer contexts, hnRNPM mediates alternative splicing of oncogenic transcripts like DIAPH3, driving hepatocellular carcinoma metastasis through epithelial-mesenchymal transition 1, and regulates SLC7A11 splicing to promote ferroptosis resistance in breast cancer 4. Disease relevance extends to neurodegeneration: polyglycine inclusions from expanded GGC repeats in NOTCH2NLC sequester hnRNPM, contributing to neuronal intranuclear inclusion disease pathogenesis 5. Additionally, hnRNPM coordinates host-viral interactions, regulating influenza A virus replication through species-specific mechanisms 6 and cisplatin resistance via BAX alternative splicing in osteosarcoma 7.