(Trp-55, Leu-133), a lid region (residues 216-239), as well as a β5 loop (residues 54-64). The ApoC-II binding site is currently unknown, but it is predicted that residues on both N-and C-terminal domains are necessary for this interaction to occur. The C-terminal domain appears to confer LPL’s substrate specificity; it has a higher affinity for large triacylglyceride-rich lipoproteins than cholesterol-rich lipoproteins. The C-terminal domain is also important for binding to LDL’s receptors. Both the N-and C-terminal domains contain heparin binding sites distal to the lipid binding sites; LPL therefore serves as a bridge between the cell surface and lipoproteins. Importantly, LPL binding to the cell surface or receptors is not dependent on its catalytic activity. The LPL non-covalent homodimer has a head-to-tail arrangement of the monomers. The Ser/Asp/His triad is in a hydrophobic groove that is blocked from solvent by the lid. Upon binding to ApoC-II and lipid in the lipoprotein, the C-terminal domain presents the lipid substrate to the lid region. The lipid interacts with both the lid region and the hydrophobic groove at the active site; this causes the lid to move, providing access to the active site. The β5 loop folds back into the protein core, bringing one of the electrophiles of the oxyanion hole into position for lipolysis. The glycerol backbone of the lipid is then able to enter the active site and is hydrolyzed. Two molecules of ApoC-II can attach to each LPL dimer. It is estimated that up to forty LPL dimers may act simultaneously on a single lipoprotein. In regard to kinetics, it is believed that release of product into circulation is the rate-limiting step in the reaction. Function LPL gene encodes lipoprotein lipase, which is expressed in the heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Through catalysis, VLDL is converted to IDL and then to LDL. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. Regulation LPL is controlled transcriptionally and posttranscriptionally. The circadian clock may be important in the control of Lpl mRNA levels in peripheral tissues. LPL isozymes are regulated differently depending on the tissue. For example, insulin is known to activate LPL in adipocytes and its placement in the capillary endothelium. By contrast, insulin has