Latent-transforming growth factor beta-binding protein 4 (LTBP4) (LTBP4)

Latent-transforming growth factor beta-binding protein 4 (LTBP4) is a structural extracellular matrix protein essential for the sequestration and regulation of transforming growth factor beta (TGF-beta) [UniProt Q99714]. It forms a complex with the latent form of TGF-beta, anchoring it to the extracellular matrix and preventing its activation until specific triggers occur [UniProt Q99714]. The hinge region of LTBP4 is a proline-rich domain that is highly susceptible to proteolytic cleavage by enzymes like plasmin and matrix metalloproteinases [Flanagan et al., 2013]. In Duchenne muscular dystrophy (DMD), polymorphisms in this hinge region or its excessive cleavage lead to the over-release of TGF-beta, which drives muscle fibrosis and impairs regeneration [Flanagan et al., 2013; Ceco et al., 2014]. Therapeutic interventions, including monoclonal antibodies, are being developed to bind and stabilize the LTBP4 hinge region, thereby preventing its degradation and reducing pathological TGF-beta signaling [Ceco et al., 2014; Hammers et al., 2020]. This targeted approach is designed to slow disease progression in muscular dystrophies and potentially other fibrotic conditions [Hammers et al., 2020].

Other names

LTBP-4Latent TGF-beta-binding protein 4Latent TGF-β binding protein 4, hinge regionLTBP4 hinge region

Stabilization of the LTBP4 hinge region to prevent proteolytic cleavage, thereby reducing the release and activation of latent TGF-beta in the extracellular matrix [Ceco et al., 2014; Hammers et al., 2020].