CLIP3 (CAP-Gly domain containing linker protein 3) is a cytoplasmic linker protein primarily involved in regulating glucose metabolism and membrane trafficking. The protein functions as a trans-Golgi network (TGN) cytoplasmic linker that localizes to the trans-Golgi apparatus and early/recycling endosomes 1. CLIP3 regulates glucose transport in adipocytes by modulating AKT kinase compartmentalization and promoting its membrane localization, which facilitates GLUT4 trafficking to the cell surface 2. This process is controlled by DHHC17-mediated palmitoylation at specific cysteine residues, which regulates CLIP3's plasma membrane association 2. CLIP3 also plays a role in insulin-regulated glucose metabolism, where insulin downregulates miR-593-3p to increase CLIP3 expression and promote glycolysis 3. Beyond metabolic functions, CLIP3 regulates TNF-α-induced apoptosis by controlling RIP1 ubiquitination through interaction with the deubiquitinating enzyme CYLD 4. Clinically, CLIP3 expression is frequently downregulated in glioblastoma, where its loss enhances stemness and glycolytic activity, promoting radioresistance 5. Additionally, altered DNA methylation at the CLIP3 locus is associated with cardiovascular disease risk in smokers 6, and CLIP3 serves as a prognostic marker in stomach adenocarcinoma 7.