ARL4C is a small GTP-binding protein that cycles between inactive GDP-bound and active GTP-bound states, regulating intracellular vesicular transport and cell migration 1. It recruits cytohesins to the plasma membrane in its GDP-bound form and regulates microtubule-dependent transport from early to recycling endosomes 2. ARL4C expression is controlled by Wnt/β-catenin and growth factor-Ras signaling pathways 13. In development, ARL4C functions as an essential regulator of tubulogenesis, orchestrating epithelial cell migration, proliferation, and differentiation 1. During hippocampal development, CRL5-mediated regulation of ARL4C stability controls pyramidal neuron migration and dendritogenesis 2. Clinically, ARL4C is significantly overexpressed in multiple cancers. In colorectal cancer, ARL4C activates RAP1/PI3K-Akt-mTOR and RAC1/Arp2/3 signaling, promoting epithelial-mesenchymal transition (EMT), invasion, and oxaliplatin resistance; targeting ARL4C with β-Lapachone restores chemosensitivity 45. In gastric cancer, high ARL4C expression correlates with peritoneal dissemination and poor prognosis through EMT activation 6. In hepatocellular carcinoma, ARL4C correlates with poor prognosis, with antisense oligonucleotides effectively inhibiting tumor growth 7. In rheumatoid arthritis, ARL4C drives fibroblast-like synoviocyte proliferation and macrophage polarization through PI3K/AKT and MAPK pathways, making it a promising therapeutic target 8.