{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRRN1, a type I transmembrane protein characterized by extracellular leucine‐rich repeats, plays diverse roles in development and disease. In human embryonic stem cells, LRRN1 is abundantly expressed on the cell surface, where it maintains self‐renewal and pluripotency by stabilizing key transcription factors (OCT4, NANOG, and SOX2) through prevention of their nuclear export via AKT‐mediated mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, aberrant LRRN1 expression has been linked to disease progression. For instance, in gastric cancer its expression is upregulated and correlates with poor prognosis; knockdown of LRRN1 promotes apoptosis by activating the Fas/FasL pathway and upregulating JUN, suggesting that LRRN1 functions to suppress cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In neuroblastoma, the role of LRRN1 appears multifaceted. On one hand, high LRRN1 expression is associated with an unfavorable outcome and supports N‐MYC–dependent growth, implicating it in oncogenic proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " On the other hand, its extracellular domain can physically interact with the ALK receptor tyrosine kinase to impair ALK phosphorylation, thus acting as an extracellular negative regulator of ALK signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, additional studies in adult cancers have identified a role for LRRN1 in promoting proliferative signals through its fibronectin type III domain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncogenesis, genetic mapping efforts have nominated LRRN1 as a candidate gene within regions linked to non‐syndromic mental retardation, thereby indicating a potential role in neurodevelopment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Consistent with this possibility, early expression analyses have identified Lrrn1 as a marker in the neuroectoderm, underscoring its involvement in the differentiation of neural progenitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, association studies in autism spectrum disorders have also implicated LRRN1 as a gene of interest in neurodevelopmental pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that LRRN1 modulates key cellular processes—including stem cell pluripotency, neural development, and tumor cell survival and proliferation—by interfacing with multiple signaling pathways and regulatory mechanisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chien-Huang Liao, Ya-Hui Wang, Wei-Wei Chang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.200"}], "href": "https://doi.org/10.1038/onc.2008.200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18591937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18591937"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shiho Hamano, Miki Ohira, Eriko Isogai, et al. 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