REEP4 is a microtubule-binding endoplasmic reticulum (ER) protein essential for proper cell division and nuclear envelope organization. During mitosis, REEP4 functions as a major determinant of ER morphology by promoting ER tubulation through its reticulon homology domain, generating the high-curvature tubular structure characteristic of mitotic ER 1. REEP4 also clears ER membranes from metaphase chr8 to prevent interference with chromosome 8 1. As part of the conserved REEP1-REEP4 subfamily, REEP4 participates in reticulophagy—the selective autophagy of ER under stress conditions 2. Beyond mitotic functions, REEP4 regulates ER morphogenesis and remodeling with roles in diverse physiological processes 3. Clinically, REEP4 variants have been implicated in focal dystonia disorders. Genetic screening identified damaging REEP4 mutations in blepharospasm and Meige syndrome patients 45, though larger cohorts and functional studies are needed to confirm causation. In reproductive health, reduced REEP4 expression in older oocytes (≥35 years) correlates with age-related chromosome 8 and aneuploidy 6. In lower-grade glioma, elevated REEP4 expression associates with poor prognosis, enhanced cell cycle signaling, and increased immune checkpoint expression 7, suggesting potential as a prognostic biomarker and therapeutic target in cancer.