 The hipposignaling pathway is a critical regulatory mechanism involved in controlling cell growth and death. It is composed of two transcription factors, Td1-4, and transcriptional co-regulators, Yp-Taz, which work together to control cellular processes such as proliferation and apoptosis. Disruption of this pathway is associated with tumor genesis and acquired resistance to therapy. Recently, researchers have developed small molecule compounds called direct surface disruptors that target the interactions between Yp and Tad proteins, providing a promising new strategy for treating cancer. This article was authored by Bin Zhao, Ajababu Vif Pabadi, Brian P. Rubin, and others.