Latent-transforming growth factor beta-binding protein 1 (LTBP1) (LTBP1)

Latent-transforming growth factor beta-binding protein 1 (LTBP1) is a large extracellular matrix (ECM) glycoprotein that plays a critical role in regulating the bioavailability of transforming growth factor-beta (TGF-beta) (UniProt: Q14766). It functions by binding to the latent form of TGF-beta (specifically TGFB1, TGFB2, and TGFB3) and anchoring it to the ECM through interactions with fibrillins and fibronectin (PubMed: 22278742, 33991472). This sequestration maintains TGF-beta in an inactive state, preventing premature signaling until it is released by mechanical stress or enzymatic cleavage (PubMed: 15184403). LTBP1 is essential for normal cardiovascular, bone, and craniofacial development, and its dysregulation is a hallmark of various pathological conditions (PubMed: 27054059, 2022183). In cancer, LTBP1 can act as either a tumor suppressor or a promoter depending on the context, while in fibrotic diseases, it facilitates the excessive TGF-beta signaling that drives tissue scarring (PubMed: 32994761, 35654775). Therapeutic strategies targeting LTBP1, such as the preclinical candidate ATYR-0101, aim to selectively modulate TGF-beta activation in the ECM to treat fibrosis and malignancy while minimizing the systemic side effects associated with broad TGF-beta inhibition (Patsnap Synapse, 2024).

Other names

LTBP-1TGF-beta1-BP-1Transforming growth factor beta-1-binding protein 1

LTBP1 modulators function by interacting with specific domains of the protein to either enhance or inhibit its activity, thereby regulating the release and activation of TGF-beta from the extracellular matrix (Patsnap Synapse, 2024). Some agents, like ATYR-0101, induce myofibroblast apoptosis through LTBP1 interaction, while others are context-specific antibodies that selectively inhibit the activation of LTBP1-associated latent TGF-beta complexes (Scholar Rock Patent, 2021).