AMY2A encodes pancreatic alpha-amylase, a hydrolase enzyme that catalyzes carbohydrate catabolism by hydrolyzing glycosyl bonds in polysaccharides 1. The enzyme contains calcium and chloride ion binding sites essential for catalytic activity and functions in the extracellular space to facilitate starch digestion [GO annotations]. AMY2A gene copy number has evolved under recent positive selection in agricultural populations consuming high-starch diets over the past 12,000 years, with duplication-containing haplotypes increasing in frequency among West Eurasians 2. Multiple independent structural variants create diverse AMY2A copy number architectures across human populations, with some showing higher-order expansions particularly in sub-Saharan Africans 3. Functionally, AMY2A copy number correlates with serum pancreatic amylase enzymatic activity; lower activity associates with increased childhood obesity risk, particularly in populations with medium-to-high starch intake 4. AMY2A variants prevalent in Arctic indigenous peoples reflect adaptation to lipid/protein-rich traditional diets, and deviation from ancestral dietary patterns can precipitate metabolic disorders 5. Clinically, elevated plasma AMY2A protein levels contribute to a multi-protein biomarker signature distinguishing gastric cancer and early gastric cancer from controls (AUC 0.930-0.998) 6. These findings highlight AMY2A's role in dietary-genetic interactions influencing carbohydrate metabolism and obesity susceptibility.