Proteomic Analysis of Hippo Pathway Protein–Protein Interactions

, 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.