SEMA7A: A glycoprotein with therapeutic potential in inflammatory diseases and tumor development

Semaphorin 7a (SEMA7A), a GPI-anchored glycoprotein with dual neuroimmune functions, has emerged as pivotal regulator of neuroinflammatory and immunopathological processes. Its biological functions are primarily mediated by stereospecific interactions between the conserved SEMA domain and two distinct receptors: plexinC1 and β1-integrin. Understanding the molecular mechanisms underlying these receptor interactions is crucial for developing targeted pharmacological interventions. This comprehensive review systematically examines recent advances in SEMA7A's structural biology and biological function. Special attention is given to the structural domains of SEMA7A and how these domains facilitate its interactions with other proteins. We focused on describing the dual immunomodulatory functions of SEMA7A in the inflammatory pathological processes under different disease conditions, including neurodegenerative disorders, immune-mediated diseases, inflammatory conditions, cardiovascular pathologies, and its oncogenic propensity in cancer progression. Furthermore, we discuss the potential clinical applications of SEMA7A modulation, focusing on its significance as a potential biomarker and target. Collectively, by highlighting the structural intricacies and interactional dynamics of SEMA7A, this review provides substantial evidence supporting SEMA7A as a viable therapeutic target and offers strategic insights for drug development targeting SEMA7A.