{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cysteine‐rich C‐terminal 1 (CRCT1) has emerged as a multifunctional molecule with diverse roles in cellular differentiation, transcriptional regulation, and disease. In esophageal squamous cell carcinoma, for instance, CRCT1 expression is downregulated in association with advanced tumor stage and lymph node metastasis, and its restoration suppresses cell proliferation while promoting apoptosis through modulation by miR‑520 g, thus functioning as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the central nervous system, CRCT1 acts as a critical coactivator for CREB‐mediated transcription; it is rhythmically expressed in the suprachiasmatic nucleus and undergoes rapid nuclear translocation in response to light, where together with CREB and CBP it stimulates period1 transcription—a process further regulated by PER2 to support circadian clock entrainment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, genetic and epigenetic studies in human blood and adipose tissue have linked CRCT1 to the regulation of energy metabolism and eating behavior, with specific polymorphisms correlating with body fat percentage and fat distribution."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Altered CRCT1 expression is also emerging as a candidate marker in head and neck malignancies; its differential transcript levels have been observed in HPV‐associated oropharyngeal squamous cell carcinomas, where it is among a panel of novel candidates with potential diagnostic value."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the realm of non‐invasive diagnostics, CRCT1 is one of four salivary exRNA biomarkers that, when combined, detect gingivitis with high sensitivity and complete specificity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In periodontal tissues, markedly higher CRCT1 expression in the periodontal ligament suggests a role in tissue differentiation and potentially in the mechanics of tooth movement"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while its upregulation in the conjunctival epithelium of patients with chronic Stevens–Johnson syndrome indicates participation in ocular surface pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, CRCT1 has been implicated in salivary gland mucoepidermoid carcinoma as a fusion partner with MAML2—fusion‐positive tumors frequently exhibiting lower histologic grade—and similar CRCT1 rearrangements (CRCT1::TRIM11) have been reported in distinct melanocytic neoplasms, thus providing diagnostic and potentially prognostic insights."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, exposure of artificial human skin tissue to intense terahertz pulses induces upregulation of CRCT1 among other epidermal differentiation complex genes, with transcriptional changes opposite to those seen in inflammatory skin diseases and cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted functions of CRCT1 in maintaining tissue homeostasis, modulating transcriptional responses to environmental cues, suppressing tumor development, and serving as a potential biomarker across a spectrum of clinical conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ning Wu, Yang Song, Liewen Pang, et al. 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