The article discusses the unusual nature of TGFβ (transforming growth factor-β) biology, particularly the temporal discontinuity between its synthesis and action, and the diverse effects it produces. The authors propose that latent TGFβ can be viewed as an extracellular sensor, where the TGFβ propeptide acts as the detector, latent-TGFβ-binding protein (LTBP) as the localizer, and TGF-β as the effector. This perspective unifies various aspects of TGFβ biology, including its secretion, storage, and activation. The sensor model explains how TGFβ responds to specific signals, such as ECM perturbations, and how these signals are relayed through different molecules like proteases, integrins, and thrombospondin (TSP). The authors also discuss the role of LTBP isoforms in differentiating TGFβ isoforms and their differential activation. They further explore how the sensor model clarifies the complex phenotypes observed in animals with defects in TGFβ signaling, such as those with null mutations in LTBP genes or Camurati-Engelmann disease, a genetic disorder affecting bone and cartilage. The article concludes by emphasizing the importance of considering latent TGFβ as a sensor in understanding its assembly, latency, activation, and activity.The article discusses the unusual nature of TGFβ (transforming growth factor-β) biology, particularly the temporal discontinuity between its synthesis and action, and the diverse effects it produces. The authors propose that latent TGFβ can be viewed as an extracellular sensor, where the TGFβ propeptide acts as the detector, latent-TGFβ-binding protein (LTBP) as the localizer, and TGF-β as the effector. This perspective unifies various aspects of TGFβ biology, including its secretion, storage, and activation. The sensor model explains how TGFβ responds to specific signals, such as ECM perturbations, and how these signals are relayed through different molecules like proteases, integrins, and thrombospondin (TSP). The authors also discuss the role of LTBP isoforms in differentiating TGFβ isoforms and their differential activation. They further explore how the sensor model clarifies the complex phenotypes observed in animals with defects in TGFβ signaling, such as those with null mutations in LTBP genes or Camurati-Engelmann disease, a genetic disorder affecting bone and cartilage. The article concludes by emphasizing the importance of considering latent TGFβ as a sensor in understanding its assembly, latency, activation, and activity.