CTNNA1 encodes α-E-catenin, a crucial component of adherens junctions that links cadherin-mediated cell adhesion complexes to the actin cytoskeleton 1. The protein associates with the cytoplasmic domains of various cadherins, particularly E-cadherin, forming complexes essential for cell-cell adhesion properties 2. Unlike initial beliefs, α-E-catenin does not directly bind F-actin when assembled in cadherin complexes, suggesting more complex mechanisms for linking adherens junctions to the cytoskeleton 2. CTNNA1 functions as an invasion-suppressor gene, with biallelic inactivation leading to increased cellular invasiveness in colon cancer, following Knudsen's two-hit model 3. The gene contains alternative transcriptional start sites that produce N-terminally truncated isoforms highly expressed in nervous tissue, potentially affecting brain-specific functions 4. Germline pathogenic variants in CTNNA1 are associated with hereditary diffuse gastric cancer (HDGC), though they account for less than 2% of HDGC families and show specific association with early-onset diffuse gastric cancer rather than lobular breast cancer 56. The protein is ubiquitously expressed across normal tissues and maps to chromosome 5 1.