Integrating machine learning potentials (MLPs) with quantum mechanical/molecular mechanical (QM/MM) free energy simulations has emerged as a powerful approach for studying enzymatic catalysis. However, its practical application has been hindered by the time-consuming process of generating the necessary training, validation, and test data for MLP models through QM/MM simulations. Furthermore, the entire process needs to be repeated for each specific enzyme system and reaction. To overcome this bottleneck, it is required that trained MLPs exhibit transferability across different enzyme environments and reacting species, thereby eliminating the need for retraining with each new enzyme variant. In this study, we explore this potential by evaluating the transferability of a pretrained ΔMLP model across different enzyme mutations within the MM environment using the QM/MM-based ML architecture developed by Pan, X. J. Chem. Theory Comput. 2021, 17(9), 5745-5758. The study includes scenarios such as single point substitutions, a homologous enzyme from different species, and even a transition to an aqueous environment, where the last two systems have MM environment that is substantially different from that used in MLP training. The results show that the ΔMLP model effectively captures and predicts the effects of enzyme mutations on electrostatic interactions, producing reliable free energy profiles of enzyme-catalyzed reactions without the need for retraining. The study also identified notable limitations in transferability, particularly when transitioning from enzyme to water-rich MM environments. Overall, this study demonstrates the robustness of the Pan et al.'s QM/MM-based ML architecture for application to diverse enzyme systems, as well as the need for further research and the development of more sophisticated MLP models and training methods.