Proteomic Analysis of Hippo Pathway Protein-Protein Interactions

The Hippo pathway is a conserved signaling cascade that regulates development, regeneration, tissue homeostasis, and organ size through a network of protein-protein interactions (PPIs). Since its discovery in Drosophila, PPI studies have significantly contributed to defining its core kinase cascade and transcriptional machinery. Over the past two decades, advances in mass spectrometry (MS)-based proteomics have transformed Hippo pathway research from targeted assays to unbiased interactome mapping, largely expanding its regulatory and functional landscapes. In this work, we introduce MS-based biochemical approaches commonly used for analyzing PPIs, summarize historical and methodological progress in characterizing Hippo-related PPIs, highlight applications of the Hippo interactome for signaling and disease studies, and discuss future directions for improving Hippo interactome-based biological discoveries and therapeutic development. Collectively, these advances establish the Hippo pathway as a valuable model for demonstrating how MS-driven interactome analysis accelerates biological research.