ODR4 (odr-4 GPCR localization factor homolog) is a conserved tail-anchored transmembrane protein that plays a critical role in G-protein-coupled receptor (GPCR) trafficking and maturation. Primary Function: ODR4 facilitates the trafficking of a subset of GPCRs from the endoplasmic reticulum (ER) to the cell surface 1. Mechanism: ODR4 functions as part of an ER-resident complex with UfSP2, physically interacting with GPCRs like the α2A-adrenergic receptor to promote their folding, maturation, and export 23. Knockdown of the human homolog C1orf27 prolongs ER-to-Golgi export kinetics by >65% and significantly inhibits surface transport of multiple GPCRs including α2A-AR, β2-AR, and D2 receptor 3. Disease Relevance: ODR4 expression is significantly elevated in lung adenocarcinoma (LUAD), where higher expression correlates with poor patient survival, suggesting potential biomarker utility 4. Additionally, ODR4 serves as a novel surface marker for circulating tumor cell (CTC) capture in metastatic triple-negative breast cancer, enhancing live CTC detection when combined with traditional markers 5. Clinical Significance: ODR4's role in GPCR biology and emerging importance as a cancer-associated surface marker indicate potential therapeutic targeting opportunities in malignancies.