Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15550674, PubMed:15364929, PubMed:16150821, PubMed:17603008, PubMed:16239926). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (By similarity). Also possesses acylglycerol transacylase and phospholipase A2 activities (PubMed:15364929, PubMed:17032652, PubMed:17603008). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (PubMed:17603008). Regulates adiposome size and may be involved in the degradation of adiposomes (PubMed:16239926). May play an important role in energy homeostasis (By similarity). 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 (By similarity). a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) a triacyl-sn-glycerol + H2O = a 1,2-diacylglycerol + a fatty acid + H(+) a triacyl-sn-glycerol + H2O = 1,3-diacyl-sn-glycerol + a fatty acid + H(+) a triacyl-sn-glycerol + H2O = a 2,3-diacyl-sn-glycerol + a fatty acid + H(+) a 1,3-diacylglycerol + a 1-acylglycerol = a triacylglycerol + glycerol a 1,2-diacylglycerol + a 1-acylglycerol = a triacylglycerol + glycerol 2 a 1-acylglycerol = a 1,2-diacylglycerol + glycerol a triacyl-sn-glycerol + all-trans-retinol = a diacylglycerol + an all-trans-retinyl ester (9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 1,3-di-(9Z-octadecenoyl)-glycerol + H(+) 1,3-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol 1,2-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol 2 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-glycerol + glycerol 1,2,3-tri-(9Z-octadecenoyl)-glycerol + all-trans-retinol = all-trans-retinyl 9Z-octadecenoate + di-(9Z)-octadecenoylglycerol 1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate + 1,3-di-(9Z)-hexadecenoylglycerol + H(+) 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)-octadecadienoate + 1,3-di-(9Z,12Z)-octadecadienoylglycerol + H(+) 1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = (9Z,12Z,15Z)-octadecatrienoate + 1,3-di-(9Z,12Z,15Z)-octadecatrienoylglycerol + H(+) 1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = 1,3-di-(9Z-octadecenoyl)-glycerol + H(+) + hexadecanoate 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 1-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H(+) 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + H(+) 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+) 1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate + 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + H(+) 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)-octadecadienoate + 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + H(+) 1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = (9Z,12Z,15Z)-octadecatrienoate + 2,3-di-(9Z,12Z,15Z)-octadecatrienoyl-sn-glycerol + H(+) 1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = (9Z)-octadecenoate + 2-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + H(+) 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+) + hexadecanoate 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-3-hexadecanoyl-sn-glycerol + H(+) a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor (PubMed:17032652). No differences in the acylglycerol transacylase was detected in the presence or absence of ATP (PubMed:15364929). Optimum pH is 7.5 with (1,2-dilinoleoyl)-phosphatidylcholine as substrate. Glycerolipid metabolism; triacylglycerol degradation. Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (By similarity). Interacts with SERPINF1; this interaction stimulates the phospholipase A2 activity of PNPLA2 (PubMed:17032652). Despite a colocalization in lipid droplets, it probably does not interact with PLIN (By similarity). Interacts with PLIN5; prevents interaction with ABHD5 (By similarity). Interacts with FAF2 (PubMed:23297223). Highest expression in adipose tissue. Also detected in heart, skeletal muscle, and portions of the gastrointestinal tract. Detected in normal retina and retinoblastoma cells. Detected in retinal pigment epithelium and, at lower intensity, in the inner segments of photoreceptors and in the ganglion cell layer of the neural retina (at protein level). Induced during differentiation of primary preadipocytes to adipocytes. Expression increased from fetal to adult in retinal pigment epithelium. Phosphorylation at Ser-404 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity (By similarity). Phosphorylation at Ser-404 is increased upon beta-adrenergic stimulation (PubMed:22733971). Genetic variations in PNPLA2 may influence plasma free fatty acids and triglycerides levels, and fasting glucose concentrations. Genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2. The disease is caused by variants affecting the gene represented in this entry. Extended N-terminus. Extended N-terminus.