Lactase-phlorizin hydrolase (LPH) is expressed only in the small intestine and is confined to absorptive enterocytes on the villi with a tightly controlled pattern of expression along the proximal to distal and crypt-villus axes of the intestine. LPH expression is regulated mainly at the level of lactase (LCT) gene transcription that directs 2 phenotypes: a decline in LCT activity (LCT nonpersistence) in mid-childhood in the majority of the world's population, and maintenance of the lactase levels found in infancy (LCT persistence) in people of northern European extraction and scattered populations elsewhere. The molecular mechanisms that regulate these phenotypes are not completely understood. A population genetic association of lactase persistence with 2 single nucleotide polymorphisms in the distal 5'-flanking region of LCT (-13.9T and -22A) has been confirmed in northern Europeans, but this fails to explain lactase persistence found in some African groups. Any hypothesis for the control of lactase expression must reconcile the presence of high levels of activity in early life in all humans and the characteristic loss of activity found subsequently in many but not all people.