SERGEF (secretion-regulating guanine nucleotide exchange factor) is a probable guanine nucleotide exchange factor (GEF) involved in cellular secretion and signal transduction. The protein localizes to the cytoplasm, cytosol, nucleus, and nucleoplasm, where it likely functions in protein secretion regulation 1. SERGEF belongs to the RCC1-related GEF family and interacts with secretory machinery proteins; downregulation of related GEF-interacting proteins increases proteoglycan secretion, suggesting SERGEF negatively regulates protein secretion 1. The gene is located on chromosome 11 and shows evolutionary conservation across eukaryotes 2. Clinically, SERGEF variants are associated with multiple disease contexts. A SNP in SERGEF (rs2023902) increases smokeless tobacco use risk among Mexican heritage youth 3. SERGEF is included in a 15-gene biomarker for distinguishing benign from malignant thyroid tumors in cytologically indeterminate cases 4. In cardiovascular research, SERGEF variants show genome-wide significant associations with carotid artery intima-media thickness and stroke risk in African American populations, potentially through local European ancestry effects 56. Additionally, SERGEF co-expresses with NFATc1 in vascular smooth muscle cells during osteogenic transformation in the osteosarcoma microenvironment, suggesting involvement in cytoskeletal remodeling 7.