Patatin-like phospholipase domain-containing protein 2 (PNPLA2) plays a key role in hydrolysis of stored triacylglecerols and is also known as adipose triglyceride lipase (ATGL) []. Members of this family share a patatin domain, initially discovered in potato tubers [, ]. ATGL is expressed in white and brown adipose tissue in high mRNA levels. Mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) leads to neutral lipid storage disease (NLSD) which is characterized by the accumulation of triglycerides in multiple tissues []. ATGL mutations are also commonly associated with severe forms of skeletal- and cardio-myopathy. ATGL is regulated by insulin []. PNPLA2/ATGL is also known as TTS-2.2 (transport-secretion protein 2.2), iPLA2-zeta (calcium-independent phospholipase A2), and desnutrin [, , ].
This entry includes patatin-like phospholipase domain-containing proteins 1-5 (PNPLA1-5) from humans and Atgl-1 from Caenorhabditis elegans. They are a group of lipid hydrolases. Atgl-1 may play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion [, , , , , ]. In humans PNPLA1 has a role in the formation of the epidermal lipid barrier; mutations in this gene are associated with the skin disorder known as ichthyosis []. PNPLA1 acts as an omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation [, ]. It catalyzes the last step of the synthesis of omega-O-acylceramides by transferring linoleic acid from triglycerides to an omega-hydroxyceramid [].Human PNPLA2 catalyses the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets []. PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities [].
