REEP3 (receptor accessory protein 3) is a microtubule-binding protein that plays critical roles in endoplasmic reticulum (ER) morphology regulation and cell division. REEP3, along with REEP4, serves as a major determinant of ER tubular morphology during mitosis, specifically promoting ER tubulation through reticulon homology domains (RHDs) to generate the high-curvature morphology characteristic of mitotic ER 1. The protein functions to clear ER membranes from metaphase chr10 during mitosis, ensuring proper nuclear envelope reassembly 1. REEP3 belongs to an evolutionarily conserved protein family involved in ER morphogenesis, microtubule cytoskeleton regulation, and G protein-coupled receptor trafficking 2. Disease associations include potential roles in autism pathogenesis through position effects on gene expression 3, contributions to cisplatin resistance in osteosarcoma 4, and correlation with poor prognosis in pancreatic cancer where elevated expression associates with immune infiltration and unfavorable survival outcomes 5. REEP3 has also been identified as a risk locus in genome-wide association studies of IgA nephropathy 6 and migraine subtypes 7, suggesting broader involvement in various pathological processes.