Targeting TSPAN4: linking migrasome function to disease pathogenesis

Tetraspanin 4 (TSPAN4) is a key member of the tetraspanin family, serving as a critical regulator of essential biological processes including cell migration, intercellular cargo trafficking, immune homeostasis, and cellular phenotypic modulation. These pleiotropic functions are primarily mediated by TSPAN4’s ability to drive migrasome biogenesis, assemble membrane signaling complexes, and orchestrate protein–protein interaction networks. Mounting evidence indicates that the dysregulated expression of TSPAN4 and its associated regulatory networks are closely implicated in the pathogenesis and progression of a broad spectrum of diseases, spanning malignancies, reproductive system disorders, cardiovascular diseases, and ocular conditions. This pathological link involves dysregulated signaling cascades, tumor microenvironment remodeling, and impaired intercellular communication. This review systematically summarizes the molecular properties and regulatory network of TSPAN4, with an in-depth analysis of its pivotal roles in cellular homeostasis and disease-specific pathogenic mechanisms. Moreover, we propose TSPAN4 as a biomarker for disease diagnosis and prognosis, as well as its potential for targeted therapy, and highlight the current research challenges and future directions, aiming to provide new insights into TSPAN4 and TSPAN4-mediated migrasomes.