MTREX (MTR4) is an ATP-dependent RNA helicase that catalyzes unwinding of RNA duplexes with 3' single-stranded RNA extensions 12. It functions as a central subunit of multiple RNA surveillance complexes including TRAMP-like, NEXT (nuclear exosome targeting), and PAXT (poly(A) tail exosome targeting) 12. MTREX directs non-coding and aberrant transcripts for exosomal degradation and participates in 3'-processing of pre-rRNA to mature 5.8S rRNA 3. Beyond its canonical exosome functions, MTREX interacts with splicing factors and transcription elongation complexes, regulating intron retention and gene expression more broadly than previously recognized 4. MTREX regulates RNA exosome subcellular localization within the nucleolus, with MTR4 depletion causing exosome translocation to the nucleoplasm 5. Functionally, MTREX participates in DNA damage response and nuclear retention of viral RNA. Clinically, MTREX expression correlates with cognitive markers in schizophrenia patients exposed to cannabis 6. MTREX also plays roles in HIV-1 latency maintenance through RNA surveillance mechanisms 78 and regulates nuclear paraspeckle-associated lncRNA degradation 9.