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, playing a crucial role in controlling distant organ homeostasis. It is involved in multiple biological processes, such as the clearance of glycosaminoglycans (GAGs) which activates intracellular signaling [5].

In gene-edited zebrafish lacking Stab2, the interaction of fibrillar supramolecular nanoparticles with the caudal vein was abrogated, providing insights into nanoparticle-endothelial cell interactions [2]. In mouse models, ApoE-Stab2-KO mice had reduced spontaneous and Western diet-associated atherogenesis. Inhibition of Stab2 by monoclonal antibodies also significantly decreased Western diet-associated atherosclerosis in ApoE-KO and Ldlr-KO mice. This was due to an anti-inflammatory switch in the plasma proteome, suppressing monocytes and protecting against atherogenesis [1]. Also, Stab2 -/- Apoe -/- male mice developed approximately 30% smaller atherosclerotic plaques than Stab2 +/+ Apoe -/- mice when fed a Western diet, indicating that reduction of Stab2 is protective against atherosclerotic plaque development [4]. Additionally, whole-exome sequencing identified rare variants in STAB2 associated with venous thromboembolic disease, with VTE-associated variants having reduced surface expression. Haploinsufficiency of stabilin-2 may increase VTE risk through elevated levels of procoagulants [3].

In conclusion, Stab2 is essential for the clearance of plasma molecules and regulation of organ homeostasis. Gene-knockout mouse models have revealed its significant role in atherosclerosis and venous thromboembolic disease, contributing to our understanding of these disease mechanisms and potentially paving the way for new therapeutic strategies targeting Stab2.