In this study, we explored CPNE3 as a novel downstream target of the YAP1/ TEADs transcription factor complex, and investigated the mechanism by which CPNE3 inhibits YAP1 ubiquitination by competitively binding to YAP1 with β-transducin repeat-containing protein (β-TRCP), which promotes proliferation, invasion, and chemoresistance in GC cells. The gene discussed is BTRC; the disease is gastric cancer.