Model of the molecular forms of lactase-phlorizin hydrolase during synthesis and processing in the human villus enterocyte. The early changes in apparent molecular size are due to glycosylation, as indicated in the diagram. Note that the two active sites are located in domains III and IV. The subsequently removed domains I and II are important for correct folding of the nascent protein. Although not indicated on this drawing, the enzyme forms a homodimer during processing. The final N terminal cleavage of a small segment is depicted by the elimination of the terminal loop in the microvillus form of the enzyme. these two human phenotypes.

The gene for human LPH, located on chromosome 2q21, comprises 17 exons and covers approximately 49 kb, giving rise to a messenger RNA (mRNA) of slightly more than 6 kb. From initiation codon to stop codon, human LPH mRNA encodes 1927 amino acids forming the complete translation product. Sequence comparisons indicate that the coding region is comprised of four homologous parts, leading to the suggestion that the gene is the product of two duplication events during evolution. The nascent protein is heavily glycosylated so that the final translation product is about 220 kDa (fig). This high molecular mass glycoprotein undergoes intracellular cleavage, dividing regions I and II from regions III and IV. The protein consisting of regions III and IV contains the two active sites and is inserted into the microvillus membrane of the enterocyte as a mature enzyme of approximately 160 kDa. The proximal portion encompassing regions I and II has no enzymatic activity, but has been shown to function in correct folding of the enzyme.