EHD2 is an ATP- and membrane-binding protein that regulates endocytic membrane trafficking and caveolae dynamics. The protein controls membrane reorganization and tubulation upon ATP hydrolysis, playing crucial roles in endocytic transport between plasma membrane and endosomes 1. EHD2 is highly enriched at cell surface-associated caveolae where it constrains caveolae at the plasma membrane and regulates their equilibrium with surface-dissociated forms 1. In adipocytes, EHD2 localizes to caveolae near cell surface-associated lipid droplets and regulates differentiation, insulin sensitivity, lipid storage, and lipolysis 2. The protein can also function as a nuclear-cytoplasmic shuttle protein, acting as a transcriptional corepressor when nuclear 3. EHD2 demonstrates complex disease relevance with context-dependent effects in cancer. In some cancers like colon and breast cancer, decreased EHD2 expression correlates with poor prognosis and promotes tumor cell migration and invasion through regulation of epithelial-mesenchymal transition markers like E-cadherin 456. However, in triple-negative breast cancer, EHD2 overexpression promotes tumorigenesis and metastasis by regulating store-operated calcium entry through stabilization of Orai1 calcium channels 7. This dual role suggests EHD2's function is highly context-dependent, making it a potential therapeutic target requiring careful consideration of cancer subtype.