Activation of GPER induces Src, MAPK, and PI3K/Akt signalling via transactivation of the epidermal growth factor receptor (EGFR) pathway.137 GPER modulates hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) signalling, which makes it an interesting receptor to target in the endothelium.106 In addition, oestrogen-GPER signalling enhances Notch-mediated epithelial-to-mesenchymal transition (EMT),106,138 a process resembling EndMT (functionally relevant in PAH, as described above). Here, EGFR is linked to pulmonary arterial hypertension.