{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTYRO3, a member of the TAM family of receptor tyrosine kinases, plays a multifaceted role in the regulation of innate immune homeostasis and cellular clearance. In several studies, TYRO3‐mediated signaling has been shown to modulate apoptotic cell uptake (efferocytosis), dampen inflammatory cytokine release, and even govern barrier‐protective responses such as those safeguarding the blood–brain barrier and renal glomeruli. In addition, TYRO3 functions as an entry factor for viruses – with evidence supporting its contribution to filovirus and Lassa virus infection – and has been implicated in autoimmune settings where abnormal ligand–receptor interactions and altered shedding of its soluble ectodomain are associated with systemic lupus erythematosus, Sjögren’s syndrome, and vascular dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the oncologic arena, TYRO3 has emerged as a potent driver of tumor progression. Numerous investigations have demonstrated that aberrant TYRO3 expression or activation promotes malignant cell survival, proliferation, and invasiveness across a broad spectrum of cancers – including melanoma, thyroid, colon, ovarian, gastric, pancreatic, bladder, and hepatocellular carcinomas. In these settings, TYRO3‐dependent signaling pathways—often engaging downstream effectors such as AKT, ERK, and Wnt/β‐catenin, as well as mediating epithelial–mesenchymal transition via transcriptional regulators like MITF and SNAI1—contribute not only to chemoresistance and metastasis but also to immune escape (including the upregulation of PD‐L1 and interference with ferroptosis). These findings underscore the potential of TYRO3 as both a prognostic biomarker and a therapeutic target in oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have further delineated the molecular underpinnings of TYRO3 function. Structural examinations have revealed a receptor ectodomain with immunoglobulin‐like folds capable of homophilic interactions and precise ligand recognition, while intracellularly, TYRO3 associates with adaptor proteins (such as RanBPM) and phosphorylates downstream substrates—including actin‐regulatory proteins—to modulate cytoskeletal dynamics. These insights, together with the emergence of small molecule inhibitors and monoclonal antibodies (and even noncanonical agonists like Galectin‑3), provide a basis for targeting TYRO3 signaling in both immunologic disorders and cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "38", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jian L Yin, Brett D Hambly, Shi S Bao, et al. 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