Substantial challenges remain, including: a) the complexity of AGE formation and cross-tissue involvement, raising concerns about therapeutic specificity; b) the potential for off-target effects when inhibiting RAGE/RhoA/ROCK in non-vascular tissues; c) a lack of evidence regarding dosing, timing, or patient selection in AAA contexts—particularly in cases with comorbidities such as diabetes; and d) the critical need for long-term safety/efficacy studies in AAA-specific models before considering clinical translation. This evidence concerns the gene RHOA and diabetes mellitus.