Atherosclerosis is a multifaceted disease characterised by chronic inflammation and vascular remodelling, leading to plaque formation and cardiovascular complications. Recent evidence highlights the critical role of epsins, a family of endocytic proteins, in the pathogenesis of atherosclerosis. This manuscript explores the multifarious functions of epsins in atherosclerosis, focusing on their involvement in angiogenesis, lymphangiogenesis, and the modulation of key signalling pathways. We discuss how epsins facilitate EndoMT through their interaction with the TGFβ signalling pathway, which contributes to vascular smooth muscle cell-like phenotypes and plaque instability. Additionally, we examine the therapeutic potential of targeting epsins, elucidating their interactions with crucial partners such as LDLR, LRP-1, and TLR 2/4, among others, in mediating lipid metabolism and inflammation. Furthermore, we highlight the promising prospects of epsin-targeting peptides and small interfering RNAs as therapeutic agents for atherosclerosis treatment. Despite these advancements, the research faces limitations, including a reliance on specific mouse models and a need for comprehensive studies on the long-term effects of epsin modulation. Therefore, future investigations should focus on elucidating the detailed mechanisms of epsin function and their implications in cardiovascular health, fostering collaborations to translate basic research into innovative therapeutic strategies. This work underscores the necessity for further exploration of epsins to unlock their full therapeutic potential in combating atherosclerosis and related cardiovascular diseases.