Loss-of-function mutations in the gene piezo-type mechanosensitive ion channel component 1 (PIEZO1), which encodes a mechanosensory nonselective cation channel triggered by oscillatory shear stress (OSS) or mechanical stretch, cause lymphatic valve and vessel defects resulting in lymphedema in mice and humans, underscoring the importance of physical cues for lymphatic integrity (2–7). Here, PIEZO1 is linked to lymphedema.