CDH1 encodes E-cadherin, a transmembrane protein essential for cell-cell adhesion in epithelial tissues 1. It maintains cell-cell contact through cadherin binding and supports pluripotent stem cell integrity and colony formation 2. Beyond adhesion, CDH1 functions as a regulatory hub in cell cycle control: as an APC/C coactivator (APC/CCDH1), it regulates protein degradation during cell cycle progression 34. During G1 entry, mTOR-mediated phosphorylation transiently inactivates CDH1, allowing PFKFB3 accumulation and metabolic shift toward glycolysis necessary for cell cycle entry 3. CDH1 mutations drive hereditary diffuse gastric and lobular breast cancer (HDGLBC), accounting for 1-3% of gastric cancers 51. Germline CDH1 mutations require 'second-hit' inactivation via promoter methylation or loss of heterozygosity to trigger tumorigenesis 1. Prophylactic total gastrectomy between ages 20-30 is recommended for CDH1 mutation carriers, with 90-100% revealing microscopic diffuse-type cancer foci 5. CDH1 polymorphisms (rs16260, rs5030625) associate with increased gastric cancer risk in Caucasians and Asians respectively 6, while showing protective effects in colorectal cancer subgroups 7. HPV16/18 E7 proteins suppress CDH1 expression through CDH1 promoter hypermethylation and upregulation of transcriptional repressor SNAI1 in cervical cancer 8.