This matters arising addresses the recently published article in BMC Medicine by Tao Y et al., entitled "Effect of intravenous urokinase vs best medicine treatment on functional outcome for patients with acute minor stroke (TRUST): a randomized controlled trial." While appreciating the rigorous methodology and important findings of the TRUST trial, we raise several points regarding optimizing urokinase dosing and treatment strategies. Specifically, we discuss the potential for optimizing urokinase dosing based on emerging evidence. Given China's extensive clinical experience with urokinase and associated cost considerations, we advocate for further research, including trials evaluating weight-based dosing strategies, to optimize urokinase thrombolytic therapy for patients with acute ischemic stroke. Such research is crucial for optimizing urokinase thrombolysis and establishing its role as a cost-effective treatment option, especially in resource-limited settings.© 2025. The Author(s).