{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStabilin‑1 (STAB1), also known as FEEL‑1 or CLEVER‑1, is a multifunctional type‑I transmembrane scavenger receptor characterized by a unique pattern of extracellular domains (including fasciclin‑like, epidermal growth factor–like, and Link modules) that enable a broad ligand‐binding repertoire. It is highly expressed on sinusoidal endothelial cells and alternatively activated (M2) macrophages in tissues such as liver, spleen, lymph nodes, and placenta. In addition to its basic role in vascular and tissue homeostasis, genetic studies have linked STAB1 to body fat distribution traits—including waist–hip ratio—and even implicated it as a candidate in neuropsychiatric conditions, while rare biallelic mutations point to an unexpected role in ferritin metabolism and hyperferritinemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, STAB1 mediates the clearance of a diverse array of ligands. Its extracellular region binds modified lipoproteins, advanced glycation end products, and key extracellular matrix proteins such as SPARC, as well as placental lactogen and phosphatidylserine‐containing apoptotic cells. Upon ligand binding, STAB1 internalizes these cargos and directs them to early endosomes, recycling compartments, or lysosomes via a complex intracellular trafficking pathway that involves classical sorting signals and adaptor proteins (for example, GGAs and the PTB domain–containing protein GULP). This receptor‐mediated endocytosis not only clears “unwanted‐self” molecules from the extracellular milieu but also regulates local tissue remodeling and intercellular signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its endocytic capacity, STAB1 plays a pivotal role in immune regulation and cell trafficking. It contributes to leukocyte adhesion and transendothelial migration—particularly promoting the recruitment of regulatory T cells—thereby shaping anti‐inflammatory responses. Moreover, by mediating “silent” clearance of tumor growth inhibitors such as SPARC and modulating cytokine profiles in monocytes and macrophages, STAB1 can influence tumor progression and metastasis. In addition, its functions extend to the control of lymphocyte homing in lymphoid organs and the regulation of myeloid responses during bacterial infections. These multifaceted roles establish STAB1 as a central regulator of immune homeostasis, inflammation, and pathological processes including cancer and infection."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Oliver Politz, Alexei Gratchev, Peter A G McCourt, et al. 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