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The plasma membrane allows the cell to sense and adapt to changes in the extracellular environment by relaying external inputs via intracellular signaling networks. One central cellular signaling pathway is the Hippo pathway, which regulates homeostasis and plays chief roles in carcinogenesis and regenerative processes. Recent studies have found that mechanical stimuli and diffusible chemical components can regulate the Hippo pathway primarily through receptors embedded in the plasma membrane. Morphologically defined structures within the plasma membrane, such as cellular junctions, focal adhesions, primary cilia, caveolae, clathrin-coated pits, and plaques play additional key roles. We here discuss recent evidence highlighting the importance of these specialized plasma membrane domains in cellular feedback via the Hippo pathway.