in the liver, bile duct, kidney, bone, intestinal mucosa and placenta. In the serum, two types of alkaline phosphatase isozymes predominate: skeletal and liver. During childhood the majority of alkaline phosphatase are of skeletal origin. Humans and most other mammals contain the following alkaline phosphatase isozymes: ALPI – intestinal (molecular mass of 150 kDa) ALPL – tissue-nonspecific (expressed mainly in liver, bone, and kidney) ALPP – placental (Regan isozyme) ALPG – germ cell Four genes encode the four isozymes. The gene for tissue-nonspecific alkaline phosphatase is located on chromosome 1, and the genes for the other three isoforms are located on chromosome 2. Intestinal alkaline phosphatase Intestinal alkaline phosphatase is secreted by enterocytes, and seems to play a pivotal role in intestinal homeostasis and protection as well as in suppressing inflammation via repression of the downstream Toll-like receptor (TLR)-4-dependent and MyD88-dependent inflammatory cascade. It dephosphorylates toxic/inflammatory microbial ligands like lipopolysaccharides (LPSs), unmethylated cytosine-guanine dinucleotides, flagellin, and extracellular nucleotides such as uridine diphosphate or ATP. Dephosphorylation of LPS by IAP can reduce the severity of Salmonella tryphimurium and Clostridioides difficile infection restoring normal gut microbiota. Thus, altered IAP expression has been implicated in chronic inflammatory diseases such as inflammatory bowel disease (IBD). It also seems to regulate lipid absorption and bicarbonate secretion in the duodenal mucosa, which regulates the surface pH. Since the 1960s intestinal alkaline phosphatase has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. The solubility of many drugs can be substantially improved by the design of phosphate prodrugs. On the intestinal mucosa the phosphate substructures are cleaved off by alkaline phosphatase and the drug is absorbed. Furthermore, anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the intestinal epithelium as due to an alkaline phosphatase triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. In cancer cells Studies show that the alkaline phosphatase protein found in cancer cells is similar to that found in nonmalignant body tissues and that the protein originates from the same gene in both. One study compared the enzymes of liver metastases of giant-cell lung carcinoma and nonmalignant placental cells. The two were similar in NH2-terminal sequence, peptide