Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation. a phenyl acetate + H2O = a phenol + acetate + H(+) An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl alcohol. an N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine + H(+) Binds 2 calcium ions per subunit. Homodimer. Heterooligomer with phosphate-binding protein (HPBP). Interacts with CLU. Plasma, associated with HDL (at protein level). Expressed in liver, but not in heart, brain, placenta, lung, skeletal muscle, kidney or pancreas. Glycosylated. The signal sequence is not cleaved. Present in two forms, form B contains a disulfide bond, form A does not. The allelic form of the enzyme with Gln-192 (allozyme A) hydrolyzes paraoxon with a low turnover number and the one with Arg-192 (allozyme B) with a high turnover number. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients. The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces. Belongs to the paraoxonase family.