This letter provides a critical analysis of the recent study by Luxán et al. (Cardiovasc Res. 2025) on the role of non-glycanated decorin in cardiac ageing. While acknowledging the importance of their findings, we identify several key areas requiring further investigation. These include: (1) the precise mechanistic origins of non-glycanated decorin accumulation in ageing endothelium; (2) the quantitative pathophysiological contribution of decorin-driven inflammation within the broader context of cardiac ageing; (3) the potential pleiotropic functions of decorin beyond inflammation; and (4) the significant translational challenges in targeting decorin-EGFR interactions. Resolving these issues is crucial for determining the therapeutic potential of modulating decorin in age-related cardiovascular pathologies.