Preclinical research has revealed that neratinib, an oral medication primarily approved for HER2-positive breast cancer, demonstrates significant promise in combating vascular inflammation and atherosclerosis. Atherosclerosis, a leading cause of cardiovascular disease globally, involves the buildup of fatty deposits and chronic inflammation in artery walls. The study, published in *Circulation Research*, found that neratinib effectively inhibited endothelial cell inflammation and attenuated atherosclerotic plaque development in both male and female mouse models. Intriguingly, neratinib's anti-inflammatory effects were found to be independent of its classical target, HER2/ERBB2 inhibition. Instead, the drug directly binds to and suppresses ASK1 (apoptosis signal-regulating kinase 1) activation, which is a key pathway in inflammatory responses and vascular disorders. This novel mechanism of action opens new avenues for targeting residual inflammatory risk in atherosclerosis, which often persists despite current cholesterol-lowering therapies like statins. Moreover, the research highlighted the synergistic potential of neratinib. When administered in conjunction with rosuvastatin, a standard lipid-lowering drug, it produced superior anti-atherosclerotic effects compared to statin monotherapy. These findings support the concept of drug repurposing, where existing approved medications are evaluated for new therapeutic uses, potentially accelerating the translation of preclinical discoveries to human clinical testing. While the results are highly promising, researchers emphasize that these are preclinical findings obtained from *in vitro* experiments and mouse models. Further studies, including human clinical trials, are crucial to determine the efficacy, safety, and optimal dosing regimens of neratinib for atherosclerosis in humans. The prevalence of cardiovascular diseases, including atherosclerosis, in India makes this research particularly relevant for the Indian audience, as it signifies a potential new therapeutic strategy for a major public health challenge. Neratinib is currently accessible in India through named patient programs for its approved breast cancer indication.