RASGEF1C (RasGEF domain family member 1C) is a guanine nucleotide exchange factor that activates Ras family small G-proteins, particularly Rap2, at the plasma membrane 1. In endothelial cells, RASGEF1C-mediated Rap2 activation antagonizes Rap1 signaling to regulate barrier resistance 1. RASGEF1C exhibits significant disease relevance across multiple pathologies. In neurodegenerative disease, RASGEF1C expression dysregulation occurs in late-onset neurocognitive disorders including Alzheimer's disease 2, and genetic variants in RASGEF1C associate with earlier amyloid deposition onset, a hallmark of early AD pathology 3. The gene contains a polymorphic (GGC)-repeat in its promoter region under natural selection in humans, with disease-associated genotypes showing significant divergence from the predominant 6-repeat allele 2. In cancer, RASGEF1C upregulation drives lung cancer progression by activating PLK1 signaling, which enhances aerobic glycolysis and promotes tumor cell proliferation, migration, and survival 4. RASGEF1C hypomethylation serves as a promising epigenetic biomarker distinguishing papillary thyroid cancer from benign nodules, with high diagnostic accuracy particularly in younger patients and BRAF V600E-positive tumors 5. Additionally, RASGEF1C variants associate with heart failure susceptibility through protein interaction networks 6, and dysregulated RASGEF1C expression correlates with preeclampsia risk 7.