{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin Y (CCNY) is emerging as a multifunctional protein with roles spanning immune regulation, cell‐cycle control, signaling modulation and tumorigenesis. Genetic studies have implicated CCNY variants as susceptibility factors in inflammatory bowel and autoimmune diseases, with association studies linking CCNY polymorphisms to both Crohn’s disease and ulcerative colitis and even to differential responses to biologic therapy (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, CCNY functions as a regulatory subunit for atypical cyclin‐dependent kinases. It activates kinases such as CDK16 (also known as PCTAIRE1) and CDK14, thereby influencing critical cell‐cycle transitions, cytokinesis and even spermatogenesis. Mechanistic studies have shown that CCNY, via phosphorylation by upstream kinases (or its own phosphorylation state), controls partner binding and kinase activity, ensuring proper cell division and autophagic responses (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CCNY is also frequently deregulated in cancer. Overexpression of CCNY is associated with enhanced proliferation, migration and invasion in various malignancies including glioma, non‐small cell lung cancer, ovarian cancer, hepatocellular carcinoma and breast cancer. In these settings, CCNY not only promotes cell‐cycle progression by partnering with kinases such as CDK4 and CDK16 but also activates signaling pathways such as noncanonical Wnt signaling that drive tumor progression (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": " In some tumor types, CCNY functions in complex with other kinases – for instance, forming a complex with PFTK1 or CDK14 to regulate Wnt pathway components during both embryonic and cancer cell mitosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the post‐translational level, CCNY is subject to complex regulatory mechanisms. Its phosphorylation at specific serine residues (e.g. Ser100 and Ser326) governs binding to adaptor proteins such as 14–3–3 and influences its association with kinase partners, as well as its ubiquitination and turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cell cycle and tumorigenesis, CCNY has been implicated in metabolic regulation. Knockout studies in mice indicate that loss of CCNY leads to lower body weight, altered adipocyte differentiation and impaired hepatic insulin signaling, thereby linking CCNY to energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Furthermore, CCNY amplification has been identified as a potential driver in metastatic lung adenocarcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n\n In the nervous system, CCNY expression in differentiated neurons has been shown to modulate genes associated with epilepsy and neurodegeneration, contributing to neuroprotection against seizure-induced injury; concomitantly, activation of CDK16 by CCNY supports receptor endocytosis and synaptic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in platelets, diminished CCNY levels have been documented in diabetic conditions as a consequence of enhanced calpain activity, suggesting a role in platelet function and activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore CCNY as a signaling hub whose genetic variants and expression levels critically influence inflammatory responses, cell‐cycle regulation, developmental processes and cancer progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andre Franke, Tobias Balschun, Tom H Karlsen, et al. 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