Stab2, also known as Stabilin-2, is a scavenger receptor preferentially expressed by liver sinusoidal endothelial cells. It mediates the clearance of various circulating plasma molecules, thus playing a crucial role in maintaining distant organ homeostasis. It is involved in the clearance of glycosaminoglycans (GAGs), apoptotic cells, and bacteria, and is responsible for the specific binding and internalization of 22 discrete molecules, macromolecular complexes, and cell types [5].

In gene-knockout (KO) mouse models, studies have shown significant impacts on disease-related processes. ApoE-Stab2-KO mice had reduced spontaneous and Western diet-associated atherogenesis, indicating that Stab2 may contribute to atherogenesis [1]. Similarly, Stab2-/-ApoE-/-males on a Western diet developed approximately 30% smaller atherosclerotic plaques, suggesting that reduction of Stab2 is protective against atherosclerotic plaque development [4]. Whole-exome sequencing in humans identified rare variants in STAB2 associated with venous thromboembolic disease, with VTE-associated variants having reduced surface expression [3]. In zebrafish, gene-edited zebrafish lacking Stabilin-2 showed abrogated interaction of fibrillar supramolecular nanoparticles with the caudal vein, demonstrating its role in nanoparticle clearance [2].

In conclusion, Stab2 is essential for the clearance of multiple molecules and plays a significant role in maintaining physiological homeostasis. KO mouse models and other functional studies have revealed its importance in diseases such as atherosclerosis and venous thromboembolic disease. Understanding Stab2's functions through these models provides insights into disease mechanisms and potential therapeutic targets for these diseases.