NOMO2 (NODAL modulator 2) is a type I transmembrane protein component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the endoplasmic reticulum lipid bilayer 12. The MPT complex functions downstream of the SEC61 complex, occluding its lateral gate to promote insertion of subsequent transmembrane regions after initial membrane insertion 2. Beyond its primary role in protein translocation, NOMO2 has emerged as a key regulator in cancer biology. NOMO2 is upregulated in radioresistant lung cancer stem-like cells and contributes to radioresistance; its depletion sensitizes cells to radiation-induced apoptosis 34. Similarly, NOMO2 downregulation by polyphyllin D correlates with apoptosis induction in triple-negative breast cancer cells 5. NOMO2 regulates chemo- and radioresistance through modulation of checkpoint kinase Chk1/Chk2 phosphorylation pathways 4. Additionally, elevated plasma NOMO2 levels predicted cognitive decline in information processing speed over a 9-year follow-up 6. NOMO2 has also been implicated in glaucoma pathogenesis and EGFR inhibitor resistance in lung cancer 78. These findings position NOMO2 as a potential therapeutic target for overcoming treatment resistance in multiple cancer types.