The Hippo pathway is a highly evolutionarily conserved protein kinase signaling pathway, which regulates cell proliferation, apoptosis, and organ morphology and size through the regulation of downstream transcriptional co-activator Yes-associated protein (YAP).85, 86, 87 As transcriptional coactivators, YAPs do not have a DNA-binding domain, and they promote downstream by interacting with the transcription factor TEADs, significantly enhancing Ezrin expression, thereby leading to the growth and progression of osteosarcoma and lung metastasis.88 This evidence concerns the gene EZR and osteosarcoma.