CLDN12 (claudin-12) is a tight junction protein that plays a critical role in sealing the intercellular space through calcium-independent cell-cell adhesion, maintaining epithelial barrier integrity across multiple tissues 1. In the peripheral nervous system, CLDN12 is essential for myelin barrier maintenance; its deficiency leads to barrier breakdown, mechanical hypersensitivity, and pain through disruption of myelin integrity and increased TNFα signaling 2. CLDN12 expression is also relevant to blood-brain barrier (BBB) function, with region-specific changes in hippocampal and cortical tissue affecting BBB integrity in epilepsy 3. Clinically, CLDN12 has significant prognostic implications across multiple cancers. Reduced CLDN12 expression predicts poor disease-specific survival in cervical cancer, serving as an independent prognostic factor 4. Conversely, in lung adenocarcinoma, CLDN12 is upregulated and associated with advanced tumor stage, lymph node metastasis, and poor outcomes; CLDN12 knockdown suppresses proliferation and migration while promoting apoptosis 5. In pancreatic adenocarcinoma, CLDN12 upregulation promotes epithelial-mesenchymal transition and cell invasion through LINC00857-mediated regulation 6. These divergent roles suggest CLDN12's context-dependent function in cancer progression, making it a potentially valuable biomarker and therapeutic target across multiple malignancies.