Latent transforming growth factor beta binding protein 1 (LTBP1): roles as a multifunctional extracellular matrix regulator in human disease - from molecular mechanisms to clinical translation prospects.

Abstract

Latent transforming growth factor beta binding protein 1 (LTBP1) is a key regulator of the extracellular matrix (ECM). However, its role as a molecular hub that integrates biochemical signals within the mechanical microenvironment across diverse human diseases has not been systematically elucidated. To address this, this review provides an in-depth analysis of the current evidence chain for LTBP1, from basic biology to disease mechanisms. The analysis indicates that through its isoforms, post-translational modifications (PTMs), and dynamic conformation, LTBP1 not only precisely modulates the spatiotemporal activity of TGF-β but also independently orchestrates ECM assembly and mediates direct cell signaling. In disease, LTBP1's function exhibits strong context-dependency: it acts as a "double-edged sword" in cancer (driving progression or suppressing growth); it serves as a key pathological mediator in fibrosis, and contributes to structural defects in cardiovascular, neurological, and developmental disorders. These mechanisms lay a solid foundation for its clinical translation: LTBP1 is established as a multidimensional biomarker and constitutes a novel target for a range of intervention strategies, from targeted therapies and cell therapies to functionalized biomaterials. In summary, establishing LTBP1 as a key pathological integrator in systematic studies, provides a new framework and direction for understanding common mechanisms of complex diseases and developing precision medicine strategies.