IER3IP1 (immediate early response 3 interacting protein 1) is an endoplasmic reticulum membrane protein that serves as a critical regulator of ER-to-Golgi trafficking and cellular homeostasis 1. The protein localizes to Rab11 vesicles and interacts with Rab11, playing an essential role in cytokinesis by regulating vesicle fusion to the advancing furrow during cell division 1. IER3IP1 is particularly important for proinsulin trafficking from the ER to Golgi in pancreatic β-cells, with loss of function resulting in threefold reduced trafficking efficiency and subsequent β-cell dysfunction 2. The protein also regulates the unfolded protein response by limiting activation of the inositol-requiring enzyme-1α and X-box binding protein 1 pathway 3. Biallelic mutations in IER3IP1 cause Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1), a rare autosomal recessive disorder characterized by severe microcephaly, early-onset diabetes, and epilepsy 4. Disease-causing mutations impair the protein's localization to Rab11 vesicles and disrupt ER-to-Golgi trafficking 1. Beyond its role in pancreatic β-cells and neurons, IER3IP1 is essential for B cell development, with hypomorphic mutations causing B cell deficiency 3. The protein also responds to cellular stress, with expression transiently increased by TNF-α through NF-κB-mediated transcriptional activation 5.