Functional network analysis identified key hub proteins including ACTR3, ACTN1, and MYH9 (actin remodeling) and F2 (coagulation).<h4>Conclusion</h4>We identified a plasma protein signature that accurately predicts progression from latent to active tuberculosis, linking disease onset to dysregulation of the actin cytoskeleton and coagulation. Here, ACTN1 is linked to tuberculosis.