THSD1 Is a Multifaceted Regulator in Health and Disease.

Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) is a transmembrane protein increasingly recognized for its critical roles in vascular biology and disease pathogenesis. Initially identified as a marker of hematopoietic stem and endothelial cells during embryogenesis, THSD1 has since been implicated in a wide spectrum of physiological and pathological processes. This paper consolidates current knowledge on THSD1, with a focus on its roles in vascular integrity, perinatal disorders, and tumorigenesis. In vascular systems, THSD1 promotes focal adhesion assembly and suppresses autophagy-mediated adhesion turnover, thereby stabilizing endothelial attachment and maintaining barrier function. Genetic and functional studies support its protective role against intracranial aneurysms and hemorrhagic vascular disorders. THSD1 mutations have also been linked to perinatal disorders such as nonimmune hydrops fetalis and congenital vascular anomalies, suggesting a broader role in embryonic vascular patterning. Moreover, emerging evidence indicates that THSD1 acts as a tumor and metastasis suppressor, with potential anti-angiogenic properties, although its role in cancer remains to be fully defined. This paper not only consolidates existing knowledge but also identifies critical research gaps, providing a robust foundation for future investigations into the biology and clinical relevance of THSD1.