{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CADM2 is a member of the immunoglobulin superfamily of cell adhesion molecules that has emerged as a pivotal regulator in both the central nervous system and in tumor suppression. In the brain, CADM2 contributes to synaptic assembly and signaling by mediating neuron–neuron adhesion, thereby influencing cognitive processing and axonal guidance. Genetic studies have linked variants near CADM2 with diverse neurobehavioral and metabolic traits, including longevity, obesity, and substance use—findings that imply CADM2 plays an important role in energy homeostasis and the behavioral regulation of reward and risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in neural function, CADM2 has been characterized as a tumor suppressor in several malignancies. Reduced expression or inactivation of CADM2 has been observed in hepatocellular carcinoma, prostate cancer, clear cell renal carcinoma, glioma, and endometrial carcinoma, where its loss is associated with enhanced cell proliferation, invasion, and poorer clinical outcomes. Mechanistically, CADM2 appears to regulate key processes such as cell cycle progression and epithelial–mesenchymal transition, potentially via modulation of intracellular signaling pathways including PI3K/AKT."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings underscore the multifaceted functions of CADM2 in regulating neuronal connectivity and influencing metabolic and behavioral phenotypes, while also acting as a critical barrier to tumor progression in a variety of tissues. The dual roles of CADM2 in both brain function and tumor suppression not only enhance our understanding of its basic biology but also point to its potential as a biomarker and therapeutic target in metabolic disorders and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Linda Broer, Aron S Buchman, Joris Deelen, et al. 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