CDH12 (cadherin 12) is a calcium-dependent cell adhesion protein that mediates homophilic cell-cell interactions and contributes to adherens junction organization 1. As a type II classical cadherin, CDH12 functions in cell-cell adhesion, junction assembly, and cell migration 2. In cancer biology, CDH12 plays a complex role in tumor progression. In colorectal cancer, CDH12 promotes proliferation, migration, invasion, and angiogenesis, with elevated expression correlating with invasion depth 2. In thyroid carcinoma, CDH12 mediates invasion and metastasis through epithelial-to-mesenchymal transition (EMT), with its expression regulated by FTO-dependent m6A methylation and IGF2BP2-mediated mRNA stability 3. However, in bladder cancer, CDH12 enrichment predicts superior response to immunotherapy despite chemoresistance, with CDH12-expressing cells exhibiting an undifferentiated, progenitor-like state and expressing PD-L1/PD-L2 4. Genetically, CDH12 variants are associated with neuropsychiatric disorders including bipolar disease, schizophrenia, and methamphetamine/alcohol dependency 1, and a CDH12 locus was identified as significantly associated with antipsychotic drug response in schizophrenia patients 5. CDH12 expression is regulated by DNA methylation in pituitary neuroendocrine tumors 6. These findings suggest CDH12 functions contextually—promoting tumor aggression in solid cancers while paradoxically enhancing immunotherapy responsiveness in bladder cancer.