TRHDE (thyrotropin releasing hormone degrading enzyme) is a metalloaminopeptidase that inactivates thyrotropin-releasing hormone (TRH) following its release, functioning as a key regulator of TRH signaling 1. The enzyme localizes to the plasma membrane and extracellular compartments, where it catalyzes peptide proteolysis and participates in cell-cell signaling 2. Beyond canonical TRH degradation, TRHDE-associated sequences generate functionally diverse non-coding RNAs. The antisense lncRNA TRHDE-AS1 acts as a competing endogenous RNA (ceRNA) and tumor suppressor across multiple cancer types. In gastric cancer, downregulated TRHDE-AS1 correlates with poor prognosis and advanced TNM staging; its overexpression inhibits cell proliferation, migration, and invasion partly through miR-1275 sequestration 1. In lung cancer, TRHDE-AS1 overexpression suppresses proliferation and invasion via the miR-103/KLF4 regulatory axis 3. TRHDE-AS1 similarly acts therapeutically in hypertrophic scarring by inhibiting fibroblast proliferation through the miR-181a-5p/PTEN axis 4. In prostate cancer, propofol-induced TRHDE-AS1 upregulation—mediated by METTL14-catalyzed m6A modification—suppresses malignancy and apoptosis evasion 5. Additionally, a TRHDE-AS1-derived peptide (pep5-nc-TRHDE-AS1) participates in mitochondrial metabolism with substantial tumor growth impacts 6. TRHDE-AS1 expression correlates with immune microenvironment composition in glioma 2, establishing TRHDE regulation as a multi-level node in cancer pathogenesis and potential therapeutic intervention.