ALYREF (Aly/REF export factor) is a critical component of the TREX complex that functions as an mRNA export adaptor and 5-methylcytosine (m5C) reader protein. ALYREF recognizes mRNPs through multivalent interactions with exon junction complexes and facilitates mRNA nuclear export by coating and compacting mRNPs into globular structures 1. As an m5C reader, ALYREF specifically binds to m5C-modified mRNAs, enhancing their stability and export from the nucleus 2. This mechanism is conserved across multiple cancer types, where ALYREF binding to m5C sites in 3'-untranslated regions stabilizes oncogenic mRNAs including PKM2 in bladder cancer 3, NDRG1 in cervical cancer 4, CDC42 in glioma 5, and ACC1 in prostate cancer 6. The protein undergoes regulated cytoplasmic-nuclear shuttling, which is disrupted by chemotherapeutic agents like paclitaxel, but can be restored through RNF31-mediated ubiquitination, contributing to drug resistance in triple-negative breast cancer 7. ALYREF also stabilizes long non-coding RNAs such as MALAT1 through m5C recognition, promoting sorafenib resistance in hepatocellular carcinoma 8. These findings establish ALYREF as a key regulator of mRNA metabolism with significant implications for cancer progression and therapeutic resistance.