{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe studies collectively reveal that DDHD2, a serine hydrolase, is critical for maintaining lipid homeostasis in the central nervous system by acting as a principal triglyceride hydrolase. Loss‐of-function of DDHD2 in mouse models leads to a dramatic accumulation of triglycerides and lipid droplets within neurons, which is associated with motor and cognitive deficits resembling complex hereditary spastic paraplegia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional evidence indicates that DDHD2 contributes to synaptic plasticity and memory formation. Genetic ablation of DDHD2 blunts the increase in saturated free fatty acids—especially myristic acid—that normally occurs during neuronal stimulation, and DDHD2 is found to interact with the synaptic protein STXBP1, which appears to regulate its targeting to the plasma membrane and its metabolic output. These findings connect impaired triglyceride metabolism catalyzed by DDHD2 with deficits in learning and memory."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, investigations in vascular endothelial cells demonstrate that DDHD2 influences lipid peroxidation and cell survival in response to radiation. Knockdown of DDHD2 in human artery endothelial cells leads to reduced levels of protective GPX4 and Nrf2 proteins, thereby promoting ferroptosis and contributing to radiation-induced atherosclerotic changes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIt is important to note that none of the provided abstracts discuss AP1B1P1; rather, they uniformly focus on DDHD2 and its pivotal roles in lipid metabolism across neural and endothelial contexts. \n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jordon M Inloes, Ku-Lung Hsu, Melissa M Dix, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1413706111"}], "href": "https://doi.org/10.1073/pnas.1413706111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25267624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25267624"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jordon M Inloes, William B Kiosses, Huajin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Contribution of the Spastic Paraplegia-Related Triglyceride Hydrolase DDHD2 to the Formation and Content of Lipid Droplets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.7b01028"}], "href": "https://doi.org/10.1021/acs.biochem.7b01028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29278326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29278326"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Isaac O Akefe, Saber H Saber, Benjamin Matthews, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s44318-024-00030-7"}], "href": "https://doi.org/10.1038/s44318-024-00030-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38316990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38316990"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xi Su, Feng Liang, Ya Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom14070879"}], "href": "https://doi.org/10.3390/biom14070879"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39062593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39062593"}]}]}]}