Hippo signalling in cellular and tissue-level metabolism across health and disease

Hippo signalling is increasingly recognised as an important regulator of metabolic adaptation rather than solely a pathway controlling organ size and growth. This review examines how nutrients, hormones, and energy stress regulate Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) activity, and how Hippo signalling, in turn, rewires glucose, lipid, amino acid, and nucleotide metabolism. We highlight emerging concepts, including metabolite-specific checkpoints, tissue-specific Hippo functions across metabolic organs, and the context-dependent roles of Hippo signalling in obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease/steatohepatitis, cardiometabolic disease, and cancer. We also discuss how this bidirectional Hippo-metabolism axis is opening new therapeutic opportunities, while underscoring that effective translation will require cell-type- and disease-stage-specific targeting.