{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSuccinate receptor 1 (SUCNR1), formerly known as GPR91, was originally identified as a G‐protein–coupled receptor for the citric acid cycle intermediate succinate, thereby establishing a direct link between cellular metabolism and systemic physiology. In several studies, activation of SUCNR1 has been shown to regulate energy homeostasis and blood pressure through renin–angiotensin pathways, as well as modulate metabolic adaptations in skeletal muscle during exercise, cardiac responses following ischemia, and pulmonary vascular tone. These observations not only underscore SUCNR1’s role as a metabolic sensor but also implicate its signaling in diverse cardiovascular and respiratory functions."}, {"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": "\nBeyond its metabolic sensing function, SUCNR1 is critically involved in modulating immune and inflammatory responses. In activated macrophages, for example, succinate release coupled with SUCNR1 up‐regulation amplifies proinflammatory cytokine production, thereby contributing to conditions such as rheumatoid arthritis. In adipose tissue, receptor activation is implicated in obesity‐driven inflammation and type 2 diabetes, while in reproductive tissues, enhanced expression in the myometrium regulates cytokine secretion and contractile responses during labor. Moreover, SUCNR1 signaling has been shown to affect retinal vascular development in retinopathy of prematurity, further highlighting its immunomodulatory and inflammatory roles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSUCNR1 activation also contributes to tissue remodeling, fibrogenesis, and cancer progression. In hepatic stellate cells, its stimulation by succinate promotes fibrogenic responses and may drive the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis. In the tumor microenvironment, succinate released by cancer cells activates SUCNR1 on local macrophages and other cells, thereby polarizing them toward tumor‐associated phenotypes that support angiogenesis, metastasis, and overall tumor growth. Furthermore, SUCNR1 signaling has been linked to hematopoietic progenitor proliferation and placental hypervascularization in gestational diabetes, reflecting its broad impact on both regenerative and oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of ocular disorders, SUCNR1 plays a protective role in the retina. Its expression in retinal pigment epithelium and associated microglia is essential for counteracting oxidative stress and maintaining retinal homeostasis, with genetic variants that affect miRNA-mediated regulation of SUCNR1 being linked to altered susceptibility to age-related macular degeneration. Such findings suggest that modulation of SUCNR1 expression and signaling could represent promising therapeutic targets for preventing or mitigating retinal degenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Weihai He, Frederick J-P Miao, Daniel C-H Lin, et al. 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