{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPNPLA7 is an evolutionarily conserved member of the patatin‐like phospholipase enzyme family that functions as an endoplasmic reticulum (ER)–anchored lysophosphatidylcholine (LPC) hydrolase. Detailed structural studies have revealed that its N‐terminal domains, including a transmembrane region and regulatory motifs, are critical for proper ER targeting and for mediating interactions with cellular organelles such as lipid droplets under conditions of elevated fatty acid flux, whereas its C‐terminal domain confers full catalytic activity towards LPC hydrolysis. In addition, PNPLA7 expression is induced in hepatic steatosis and exhibits a positive correlation with plasma triacylglycerol levels, suggesting a link to lipid homeostasis, although its specific contribution to very-low-density lipoprotein secretion remains to be elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in lipid catabolism, PNPLA7 plays a key part in metabolic regulation within the liver by controlling the production of glycerophosphocholine (GPC)—a precursor for endogenous choline that feeds into the methionine cycle. In PNPLA7-deficient contexts, hepatic GPC and choline levels drop markedly, recapitulating features of methionine shortage. Moreover, in immune cells such as macrophages, PNPLA7 is highly expressed under basal conditions but is downregulated upon lipopolysaccharide (LPS) stimulation; this downregulation is associated with enhanced M1 polarization, while forced overexpression suppresses proinflammatory gene expression by modulating Sirtuin1 (SIRT1)/NF-κB and p38 MAPK pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies further suggest that PNPLA7 may have clinical relevance beyond metabolic and inflammatory processes. Certain polymorphisms in the PNPLA7 gene appear to be linked to menstrual disorders in women of reproductive age, particularly in individuals with specific blood types, supporting a potential combined genetic influence on reproductive health. In parallel, a significant down-regulation of PNPLA7 in colorectal and gastric tumors has been observed, with lower expression levels correlating with reduced overall survival, indicating that PNPLA7 might serve as a valuable diagnostic and prognostic marker in gastrointestinal cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christoph Heier, Benedikt Kien, Feifei Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The phospholipase PNPLA7 functions as a lysophosphatidylcholine hydrolase and interacts with lipid droplets through its catalytic domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.792978"}], "href": "https://doi.org/10.1074/jbc.M117.792978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28887301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28887301"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiuyun Wang, Min Guo, Qian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Patatin-Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.31161"}], "href": "https://doi.org/10.1002/hep.31161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32103509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32103509"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sayaka Harada, Yoshitaka Taketomi, Toshiki Aiba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Lysophospholipase PNPLA7 Controls Hepatic Choline and Methionine Metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom13030471"}], "href": "https://doi.org/10.3390/biom13030471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36979406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36979406"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zheng Zhao, Christoph Heier, Huimin Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Patatin-Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1/NF-κB and p38 MAPK Pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms232314983"}], "href": "https://doi.org/10.3390/ijms232314983"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36499308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36499308"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Y Su, G L Kong, Y L Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation analysis of the PNPLA7 gene polymorphism and susceptibility to menstrual disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Mol Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4238/2015.March.6.20"}], "href": "https://doi.org/10.4238/2015.March.6.20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25867316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25867316"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yang Bai, Kunlun Luo, Weixuan Xie "}, {"type": "b", "children": [{"type": "t", "text": "The phospholipase PNPLA7 functions as a positive indicator in human colorectal and gastric cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000035279"}], "href": "https://doi.org/10.1097/MD.0000000000035279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37861523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37861523"}]}]}]}