FGD6 (FYVE, RhoGEF and PH domain containing 6) is a guanine nucleotide exchange factor that likely activates CDC42 by facilitating GDP-GTP exchange, thereby regulating actin cytoskeleton organization and cell morphology. FGD6 localizes primarily to the nucleus and participates in trans-Golgi network dynamics 1. In hepatic stem cells, FGD6 inhibition promotes differentiation toward a hepatocyte phenotype, as FGD6 knockdown increases albumin expression while decreasing alpha-fetoprotein 2. In pancreatic ductal adenocarcinoma, FGD6 is upregulated under low amino acid conditions through a YY1-dependent mechanism and promotes macropinocytosis and tumor growth by enhancing growth factor receptor membrane localization, particularly TGF-beta receptors 1. Genetically, FGD6 has been identified as a conserved longevity gene in mice and Caenorhabditis elegans 3, and multivariate genomic analysis identified FGD6 as a novel locus influencing healthspan, lifespan, and longevity 4. Notably, a missense variant (p.Lys329Arg) in FGD6 significantly increases polypoidal choroidal vasculopathy risk (OR=2.12) by promoting abnormal retinal vessel development, particularly in response to oxidized phospholipids 5. FGD6 expression is dysregulated in gastric cancer and pancreatic adenocarcinoma, where high expression correlates with poor prognosis 16, suggesting potential therapeutic targeting opportunities.