Model of lipid release from caveolae in response to cell stress. Schematic of the release of the cavin coat and enriched lipids from caveolae in response to cell stress. Our model proposes that caveolae, signaling proteins clustered on the PM outside of caveolae, and the lipids that make up the PM are in a “baseline/normal” state. However, upon exposure of the cell to an external stressor, such as an increase in membrane tension, caveolae are disassembled (Sinha et al., 2011); we hypothesize that this is a consequence of the release of the cavin coat complex and loss of the stability of the caveolar microdomain (McMahon et al., 2019; Sinha et al., 2011), which in turn releases the lipids enriched within the curved caveolar domain (Ariotti et al., 2014). Destabilization and release of caveolar lipids into the bulk membrane can indirectly affect protein clustering by modulation of the lipid nanoenvironment (as shown for PtdSer and Ras proteins) to modulate cellular signaling cascades (Ariotti et al., 2014). Finally, we hypothesize that this process may help cells respond to challenges from a wide array of cellular stressors (Table 1).