The article discusses the role of latent TGFβ as an extracellular sensor that responds to environmental signals, such as ECM changes, to release active TGFβ. TGFβ is secreted as a latent complex, consisting of TGFβ, LAP (latent TGFβ-binding protein), and LTBP (latent TGFβ-binding protein). The complex is stored in the ECM and is activated by various stimuli, including proteases, thrombospondin-1, integrins, reactive oxygen species, and changes in pH. The sensor model suggests that the latent TGFβ complex functions as a sensor that detects ECM perturbations and releases TGFβ in response. The components of the complex—TGFβ as the effector, LTBP as the localizer, and LAP as the detector—work together to regulate TGFβ activity. The model provides a framework for understanding TGFβ biology, including its secretion, sequestration, and activation. The study highlights the importance of the sensor model in clarifying the complex and varied nature of TGFβ activity, as well as its role in various physiological and pathological processes. The article also discusses the implications of mutations in TGFβ-related genes, such as those involved in the Camurati-Engelmann disease, and the role of the sensor model in understanding these conditions. Overall, the study emphasizes the importance of the latent TGFβ complex as a dynamic sensor that responds to environmental cues to regulate TGFβ activity.The article discusses the role of latent TGFβ as an extracellular sensor that responds to environmental signals, such as ECM changes, to release active TGFβ. TGFβ is secreted as a latent complex, consisting of TGFβ, LAP (latent TGFβ-binding protein), and LTBP (latent TGFβ-binding protein). The complex is stored in the ECM and is activated by various stimuli, including proteases, thrombospondin-1, integrins, reactive oxygen species, and changes in pH. The sensor model suggests that the latent TGFβ complex functions as a sensor that detects ECM perturbations and releases TGFβ in response. The components of the complex—TGFβ as the effector, LTBP as the localizer, and LAP as the detector—work together to regulate TGFβ activity. The model provides a framework for understanding TGFβ biology, including its secretion, sequestration, and activation. The study highlights the importance of the sensor model in clarifying the complex and varied nature of TGFβ activity, as well as its role in various physiological and pathological processes. The article also discusses the implications of mutations in TGFβ-related genes, such as those involved in the Camurati-Engelmann disease, and the role of the sensor model in understanding these conditions. Overall, the study emphasizes the importance of the latent TGFβ complex as a dynamic sensor that responds to environmental cues to regulate TGFβ activity.