{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTFCP2L1, a member of the TFCP2/Grainyhead family of transcription factors, is critical for maintaining pluripotency and self‐renewal in embryonic stem cells. In mouse ESCs, TFCP2L1 directly binds promoters such as that of Esrrb to sustain a naïve pluripotent state, whereas in human ESCs it promotes self‐renewal by selectively enhancing Klf4 expression and suppressing differentiation toward definitive endoderm and mesoderm. Its activity is modulated by post‐translational modifications—for example, CDK1 phosphorylation of TFCP2L1 orchestrates cell cycle progression and pluripotency, and has been shown to promote aggressive, stem‐like features in bladder cancer cells. In the context of germ cell fate, TFCP2L1 has been demonstrated to enhance primordial germ cell–like cell (PGCLC) specification in mouse, although in human PGCLC induction its role appears nonessential relative to other naïve factors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTFCP2L1 deregulation contributes to oncogenesis in several tissues. Its aberrant activation—for example, through CDK1-mediated phosphorylation—can stimulate tumor cell proliferation, self-renewal, and invasion, as observed in bladder cancer models. Conversely, loss of TFCP2L1 expression in renal epithelial cells is associated with transcriptional reprogramming toward oncogenic and ferroptosis-resistant states that accompany epithelial-to-mesenchymal transitions in renal medullary carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in stem cell biology and tumorigenesis, TFCP2L1 (also known as CRTR-1 or LBP-9) participates in tissue-specific transcriptional regulation. In the human placenta, TFCP2L1 interacts with related CP2-family members to modulate the expression of key steroidogenic enzymes such as P450scc, thus contributing to the regulation of placental function. In the peripheral nervous system, TFCP2L1 is subject to post-transcriptional regulation by miR708-5p, which impacts Schwann cell migration and the transcriptional activation of myelin protein promoters. Moreover, studies in other tissues have revealed that the transcriptional activity of CRTR-1 is context dependent and can be modulated by sumoylation, highlighting the multifunctional and dynamic nature of TFCP2L1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hongwei Sun, Yu You, Mengmeng Guo, et al. 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