{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTREML1, commonly referred to as TLT‐1, is a member of the triggering receptor expressed on myeloid cells (TREM) family that is uniquely expressed in platelets and megakaryocytes. Its extracellular region comprises a single immunoglobulin‐like V‐set domain, and its cytoplasmic tail contains immunoreceptor tyrosine‐based inhibitory motifs (ITIMs) (with splice variants that lack these motifs), endowing it with the potential to modulate intracellular signals in a non‐classical, co‐stimulatory manner. TLT‐1 is stored in platelet α‐granules and is rapidly translocated to the platelet surface upon activation. In addition, a soluble form of the receptor (sTLT‐1) is released during platelet activation, with structural studies revealing homology to related immunoglobulin receptors, further indicating an autonomous functional role."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, TLT‐1 plays a critical role in hemostasis and the regulation of inflammation. By binding fibrinogen, it facilitates platelet aggregation at sites of vascular injury, a function underscored in sepsis models where elevated levels of sTLT‐1 correlate with disseminated intravascular coagulation and improved survival when administered therapeutically. Moreover, studies in TLT‐1 knockout mice and patients with platelet disorders demonstrate that deficiency in TLT‐1 impairs platelet aggregation and prolongs bleeding times while exacerbating inflammatory cytokine production, suggesting that TLT‐1 serves a protective role by dampening excessive leukocyte activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in platelet function, TLT‐1 has been implicated in a spectrum of inflammatory and thrombotic disorders. Variants in the TREM gene cluster have been linked to diseases such as Alzheimer’s, while elevated TLT‐1 expression and its soluble form have been associated with atherosclerosis, acute coronary syndromes, and preeclampsia. Proteomic mapping has identified several interactors—including integrins, adaptor proteins, and kinases—that connect TLT‐1 to broader signaling pathways involved in cell adhesion, migration, and cytokine production. TLT‐1 also participates in platelet–monocyte aggregate formation in conditions such as tuberculosis and severe burns, and its deficiency has been associated with preterm birth and impaired vascular responses, collectively underscoring its importance as an endogenous regulator of inflammation and thrombosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jill W Ford, Daniel W McVicar "}, {"type": "b", "children": [{"type": "t", "text": "TREM and TREM-like receptors in inflammation and disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.coi.2009.01.009"}], "href": "https://doi.org/10.1016/j.coi.2009.01.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19230638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19230638"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexander D Barrow, Emmanuelle Astoul, Andres Floto, et al. 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