{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ABI3BP is an extracellular matrix protein that has emerged as a multifunctional regulator in diverse biological processes. In the context of neuropsychiatric disorders, a common single‐nucleotide variant in the ABI3BP locus has been associated with major depression and suicide risk, suggesting a role in mood regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In several studies of cancer, particularly thyroid, gallbladder, and esophageal carcinomas, reduced ABI3BP expression has been correlated with increased transforming activity, enhanced cell proliferation, migration, and invasion. Conversely, re‐expression of ABI3BP in thyroid cancer cell lines triggers cellular senescence via the p21 pathway and markedly suppresses tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In gallbladder cancer, ABI3BP is tightly regulated by the long noncoding RNA MALAT1 through recruitment of EZH2, and restoration of ABI3BP contributes to cell growth suppression and senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In non-malignant settings, ABI3BP plays an essential role in stem and progenitor cell biology. In mesenchymal stem cells, ABI3BP forms extracellular deposits that are critical for the cellular switch from proliferation to differentiation. Loss of ABI3BP results in stabilization of focal adhesions and enhanced proliferation, while its presence is necessary for proper osteogenic and adipogenic differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in cardiac progenitor cells, genetic ablation of ABI3BP inhibits differentiation, increases proliferative capacity, and is associated with impaired post-infarction recovery, indicating its importance in promoting cell maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, genetic studies have implicated ABI3BP in several non-cancer pathologies. In Kashin–Beck disease, copy number variations and upregulation of ABI3BP are associated with disease susceptibility"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and in a mouse model of cigarette smoke-induced emphysema, deleterious variants and differential expression of Abi3bp point to its contribution to lung tissue susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In esophageal cancer, downregulation of ABI3BP—mediated in part by oncogenic microRNA activity—leads to enhanced proliferation, migration, and invasion, reinforcing its tumor suppressor role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although in vitro studies and cellular models highlight ABI3BP’s roles in promoting senescence and regulating differentiation, whole-animal knockout studies in mice have not recapitulated strong tumor suppressive or behavioral phenotypes, suggesting the possibility of compensatory mechanisms in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Emerging evidence also links ABI3BP to the regulation of extracellular matrix dynamics and associated signaling pathways in other diseases. For example, differential splicing events affecting ABI3BP have been observed in osteoarthritis, where ABI3BP contributes to the maintenance of cartilage homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Similarly, genome-wide association studies in NSAID-induced acute urticaria and integrated miRNA/mRNA analyses in rheumatoid arthritis have implicated ABI3BP in pathways related to Ca²⁺, cAMP, and p53 signaling, underscoring its role in inflammation and tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ABI3BP functions as a key extracellular mediator involved in regulating the balance between cellular proliferation and differentiation, promoting senescence in cancer cells, and maintaining extracellular matrix integrity. Its dysregulation is associated with a broad spectrum of pathological conditions, ranging from mood disorders and various cancers to degenerative and inflammatory diseases, highlighting its potential as a biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Roy H Perlis, Jie Huang, Shaun Purcell, et al. 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