The lipid bilayer plays an important role in compartmentalization and organization of the intracellular environment and various organelles necessary for homeostatic and specialized functions. The plasma membrane is a semi-permeable barrier that provides protection from the extracellular environment and localizes membrane receptors and ion channels involved in signal transduction. Particular examples of membrane microdomains such as lipid rafts and caveolae have been studied in the context of localization of these signaling receptors and ion channels. But, very few researchers associate the plasma membrane, and its varied lipid-ordered domains, as a specialized cellular organelle important in regulating cellular metabolism and extracellular environment to cell/organelle communication. Caveolins, the structural proteins essential for caveolae formation, are present in three isoform. Although the caveolin proteins are expressed ubiquitously, their level of expression varies among different tissues. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in endothelial cells, adipocytes, and smooth muscle cells, while caveolin-3 (Cav-3) is predominantly found in striated (skeletal and cardiac) and smooth muscle. Caveolins were originally discovered as critical proteins for the formation of caveolae in cholesterol and phospholipid membrane (lipid) raft domains. Many studies have focused on the function of caveolins as signaling scaffolds within plasma membrane caveolae and lipid rafts. However, evidence in recent years indicates that caveolin proteins can have roles independent of caveolae and may functionalize caveolae in the regulation of intracellular organelles such as mitochondrial (Figure 1A-D) and allow for stress adaptation by regulation of cellular activities, including lipid transport, gene expression, and mitochondrial function. Many independent actions of caveolins may be facilitated by their presence in other cellular membranes, including: exocytic and endocytic vesicle, the endoplasmic reticulum (ER), the Golgi complex, mitochondria, the nucleus, endosome, lysosomes, peroxisomes, and lipid droplets. Functions of caveolin at such cellular locations, the interaction of membrane caveolae with mitochondria, and the mechanisms involved in intracellular caveolin trafficking are important considerations in the regulation of cell biology. This talk will specifically focus on the ability of caveolins/caveolae to communicate with and modulate the function of intracellular organelles and the impact of this communication on cell and organ physiology.