AMY2B encodes a third human alpha-amylase isozyme distinct from the salivary (AMY1) and pancreatic (AMY2A) forms 1. The gene consists of ten exons with high sequence homology to AMY1 and AMY2, featuring a more distant upstream promoter 1. AMY2B is constitutively expressed in healthy humans, with the encoded protein (HXA) detected in urine at approximately 1:5.4-4.1 molar ratios relative to pancreatic amylase 2. HXA possesses characteristic catalytic properties distinguished by distinctive peptide sequences (LVGLLDLALEKDYVR) and exhibits altered substrate specificity compared to salivary and pancreatic amylases 3. Functionally, AMY2B catalyzes alpha-1,4-glycosidic bond hydrolysis in carbohydrate metabolism through calcium and metal ion binding 23. Evolutionary analyses reveal AMY2B underwent single-origin duplications, with copy number increases correlating with agricultural adoption in human populations over the past 12,000 years, suggesting positive selection 4. Similar patterns appear in dogs, where AMY2B copy number expansion (median 11 copies versus 3 in wolves) enabled starch-rich diet adaptation following agriculture's global spread 56. The gene exhibits genomic instability with recurrent rearrangements 7, reflecting its role in human and canine dietary evolution.