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In this study, we employed Mendelian randomization analysis utilizing proteomic, transcriptomic, and metabolomic data to identify potential therapeutic targets for BrS. Our findings indicate that N-palmitoylglycine (PalGly) is linked to an increased risk of BrS and interacts with BrS-associated proteins, demonstrating moderate binding affinities for proteins such as DCC, CR1, CTSB, NAAA, DEFB1, EPHA1, IGF1/IGFBP3/ALS, and LTA. Although PalGly does not interact with Nav1.5, it enhances calcium sparks in ventricular cardiomyocytes. We determined that the calcium-modulating effect of PalGly is mediated by its binding to and activation of the transient receptor potential channel 5 (TRPC5) channel. Furthermore, PalGly was found to shorten the QT interval and action potential duration in Langendorff-perfused rabbit hearts and ventricular cardiomyocytes. Transcriptomic and lipidomic analyses of PalGly-treated neonatal rat cardiomyocytes revealed significant modulation of immune pathways, akin to the effects observed with TRPC5 agonists. Collectively, our study underscores the involvement of PalGly and TRPC5 in the pathophysiology of BrS. Overall design: To investigate the cardiac effect of N-palmitoylglycine, we extracted neonatal rat cardiomyocytes and stimulated these cells with 1 μM N-palmitoylglycine 24h hours."],"repository":["ENA"],"description_synonyms":["Cation Channels, Risk, ST Segment Elevation, sudden unexpected nocturnal death syndrome., Channels, Proteins, Risks, Brugada ECG Pattern, Sudden Unexplained Death Syndrome, TRP, TRP Cation Channel, Brugada, TRP Cation Channels, and Sudden Death Syndrome, TRP Membrane Proteins, Transient Receptor Potential Cation Channels, Relative, Transient Receptor Potential Cation Channel, Channel, Brugada Syndrome 1, Transient Receptor Potential Channel, Sudden Unexplained Nocturnal Death Syndrome (SUNDS), TRP Cation, Sudden Unexplained Nocturnal Death Syndrome, Relative Risks, Brugada Type ECG Pattern, Membrane Proteins, Cation Channel, LIPID N-palmitoyl glycine, TRP Membrane, Right Bundle Branch Block, ECG Pattern, N-palmitoyl glycine, Relative Risk"],"name_synonyms":["Cation Channels, Risk, ST Segment Elevation, sudden unexpected nocturnal death syndrome., Channels, Proteins, Risks, Brugada ECG Pattern, Sudden Unexplained Death Syndrome, TRP, TRP Cation Channel, Brugada, TRP Cation Channels, and Sudden Death Syndrome, TRP Membrane Proteins, Transient Receptor Potential Cation Channels, Relative, Transient Receptor Potential Cation Channel, Channel, Brugada Syndrome 1, Transient Receptor Potential Channel, Sudden Unexplained Nocturnal Death Syndrome (SUNDS), TRP Cation, Sudden Unexplained Nocturnal Death Syndrome, Relative Risks, Brugada Type ECG Pattern, Membrane Proteins, Cation Channel, LIPID N-palmitoyl glycine, TRP Membrane, Right Bundle Branch Block, ECG Pattern, N-palmitoyl glycine, Relative Risk"],"additional_accession":[]},"is_claimable":false,"name":"N-Palmitoylglycine activates transient receptor potential channel 5 and increases the risk of Brugada syndrome","description":"N-Palmitoylglycine activates transient receptor potential channel 5 and increases the risk of Brugada syndrome","dates":{"last_updated":"2025-09-24","first_public":"2024-10-07"},"accession":"PRJNA1167235","cross_references":{"GEO":["GSE278421"],"taxon":["10116"]}}