CYTH3 (cytohesin 3) is a guanine nucleotide exchange factor that promotes ARF1 and ARF6 activation by facilitating GTP binding 1. The protein functions in membrane trafficking, vesicle transport, and epithelial cell polarity establishment through its role in activating ADP-ribosylation factors, which regulate actin cytoskeleton rearrangements and G protein-coupled receptor internalization 1. In disease contexts, CYTH3 has emerged as a clinically relevant biomarker. In ovarian cancer, CYTH3 ranked among the most important features in machine learning models predicting cisplatin chemosensitivity and overall survival 2. In liver fibrosis, upregulation of CYTH3 promotes hepatic stellate cell activation and collagen deposition through a competing endogenous RNA mechanism involving the lncRNA Neat1 and microRNAs miR-148a-3p and miR-22-3p; CYTH3 knockdown attenuated fibrosis progression 3. CYTH3 also functions in breast cancer metastasis, where the lncRNA H19 modulates CYTH3 expression to regulate cell migration and epithelial-mesenchymal plasticity 4. Additionally, genetic variants in the CYTH3 3' untranslated region associate with protection against Shigella-associated diarrhea in infants, potentially through effects on bacterial type 3 secretion system activity 5. DNA methylation changes in CYTH3 were identified in children exposed to gestational diabetes, linking epigenetic modifications to metabolic risk 6.