Members of this family share a patatin domain, initially discovered in potato tubers, and are known as patatin-like phospholipase domain containing proteins (PNPLA). They serve critical roles in diverse aspects of lipid metabolism and signaling. Some PNPLA1 proteins do not have the lipase consensus sequence Gly-X-Ser-X-Gly which is essential for hydrolase activity. This entry includes PNPLA1 from Homo sapiens and Gallus gallus. It is expressed in various human tissues in low mRNA levels [, ].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 [].
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 [].
