TMEM204 is a transmembrane protein involved in vascular and cellular junction regulation. Primary function: TMEM204 modulates paracellular permeability and cell-cell interactions through adherens junctions 1, with structural characteristics of four transmembrane-spanning proteins that localize to cell-cell junctions 2. As a tetraspan protein, it influences vascular endothelial integrity; suppression of TMEM204 transcript expression reduces pro-apoptotic and pro-inflammatory responses in microvascular endothelial cells 3. Mechanism: TMEM204 disrupts vascular integrity when expressed, contributing to endothelial dysfunction 3. In developing endothelium, TMEM204 expression marks a population of circulating endothelial cells enriched in cancer patients, suggesting roles in both embryonic angiogenesis and adult tumor vessel development 2. Disease relevance: TMEM204 is hypermethylated in pancreatic cancer (95% of cell lines) and breast cancer, with methylation-mediated silencing serving as an epigenetic alteration 45. A TMEM204 CpG site showed association with all-cause mortality in breast cancer 5. SNPs near TMEM204 associate with lamotrigine-induced skin rash susceptibility in epilepsy patients 6. Clinical significance: TMEM204 represents a potential biomarker for cancer prognosis and therapeutic target, with epigenetic regulation relevant to cancer disparities and tumor progression.