RTN3 (reticulon 3) is an endoplasmic reticulum (ER) membrane protein that plays crucial roles in ER tubular network formation and cellular quality control mechanisms 1. The protein shapes tubular ER structures and participates in reticulophagy, a selective autophagy process that degrades ER components 23. RTN3 functions in organelle-specific autophagy pathways that are beneficial for inflammatory disorders by eliminating damaged organelles and maintaining cellular homeostasis 1. In disease contexts, RTN3 demonstrates tissue-specific effects: increased expression contributes to nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway and causing mitochondrial dysfunction 4, while RTN3 interacts with BACE1 to modulate amyloid-β formation in Alzheimer's disease pathogenesis 5. Conversely, RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through disruption of mitochondrial stability via the RTN3-HSPA9-VDAC2 complex 6. RTN3 also participates in unconventional protein secretion during cellular stress, forming ER tubular bodies that facilitate Golgi-independent trafficking 3. Additionally, RTN3 is involved in viral replication processes and can be targeted by tumor-derived exosomal miRNAs to promote macrophage M2 polarization in cancer metastasis 7.