Molecular cloning has identified three distinct caveolin genes: caveolin-1, caveolin-2, and caveolin-3. Caveolin-1 and caveolin-2 have been mapped to a common locus in chromosome 7q31.1, that is a possible candidate for a tumor suppressor gene postulated in this region. Caveolin-1 assumes an unusual topology. A central hydrophobic domain is thought to form a hairpin-like structure within the membrane. As a consequence, both the N-terminal domain and the C-terminal domain face the cytoplasm, thereby forming a caveolin-rich scaffold. Caveolin-1 and caveolin-2 proteins interact with themselves to form homo- and hetero-oligomers and are thought to be the driving force for caveolae formation. They are most abundantly expressed in adipocytes, endothelial cells and fibroblastic cell types, whereas caveolin-3 is muscle-specific. Both in vitro and in vivo experiments show the transformation suppressor activity of caveolin-1, indicating that caveolin-1 may provide a necessary brake in signal transduction. The targeted disruption of caveolin-1 in mice results in impaired nitric oxide and calcium signaling in the cardiovascular system, and displays thickening of alveolar septa caused by uncontrolled endothelial cell proliferation. Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. Caveolin-2-null phenotypes are identical to the ones that have been reported for caveolin-1-null mice in lung function. Caveolin-3 is a component of the dystrophin complex, and might be relevant to Duchennes and other muscular dystrophies. The loss of caveolin-3 expression in mice is sufficient to induce a molecular program leading to cardiac myocyte hypertrophy and cardiomyopathy.