Rabep2, or RAB GTPase-binding effector protein 2, is involved in endosomal trafficking. It interacts with the small GTPase Rab4 and regulates vascular endothelial growth factor receptor-2 (VEGFR2) endosomal trafficking, which is crucial for VEGF signaling in endothelial cells [3]. It also has a role in arteriogenesis and is a primed substrate for Glycogen Synthase kinase-3 (GSK3) [2,3].

Gene knockout mouse models have been used to study Rabep2. Deletion of Rabep2 in mice leads to decreased collateral vessel connections and increased infarct volume after ischemic stroke, indicating its importance in stroke outcomes [1]. In adult mice, deletion of Rabep2 inhibits hypoxia-induced coronary collateral formation, while knockdown of Rabep2 in endothelial cells impairs cell migration [4]. Hypoxia-preconditioned bone marrow mesenchymal stem cells can improve cerebral collateral circulation and stroke outcome in mice through upregulating Rabep2 [5]. Also, the rs11645302 polymorphism of Rabep2 is linked to poorer collateral circulation in patients with anterior circulation large artery occlusion [6].

In conclusion, Rabep2 is a key regulator in endosomal trafficking, especially for VEGFR2-dependent signaling. Its role in collateral vessel formation makes it relevant to ischemic stroke and other vascular-related diseases. Mouse models, especially gene knockout models, have been instrumental in uncovering these functions, providing insights into potential therapeutic targets for ischemic stroke and understanding the genetic factors affecting collateral development.