The LCT intron 2 region is evolutionarily conserved across mammals and exhibits age-dependent increases in DNA methylation in both mice and humans, indicating it functions as a fundamental, ancient regulatory element for lactase downregulation after weaning, independent of human-specific lactase persistence variants.

As mammals age after weaning, a specific region inside the lactase gene becomes covered with chemical tags that block its activity. This region acts like a switch that keeps the lactase enzyme being made. When the switch gets turned off by these tags, the body stops producing lactase, so milk sugar can no longer be digested. This switch is the same in mice and humans and has been preserved for millions of years because it controls a vital change in diet after infancy.