NOMO3 (NODAL modulator 3) is a multi-pass transmembrane protein that serves dual functions in cellular biology. Its primary role is as a component of the multi-pass translocon (MPT) complex, which mediates insertion of multi-pass membrane proteins into the endoplasmic reticulum membrane by occluding the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions 1. Additionally, NOMO3 functions as a negative regulator of Nodal signaling, a pathway critical for embryonic development and left-right asymmetry determination. Studies demonstrate that NOMO proteins, including NOMO3, are downregulated in facial asymmetry, suggesting their role in proper developmental patterning 2. NOMO3 expression is significantly reduced in skeletal disorders when GDF6 expression is decreased 3. In cancer contexts, NOMO3 shows high and specific expression in medullary thyroid cancer, indicating potential as a tumor-associated antigen 4. The protein also contributes to chemotherapy and radiotherapy resistance in lung cancer through involvement with checkpoint kinase pathways 5. These findings establish NOMO3 as a multifunctional protein with roles in membrane protein insertion, developmental signaling regulation, and cancer biology, making it a potential therapeutic target.