Target intelligence / Profile preview

1-acylglycerol-3-phosphate O-acyltransferase 5 (AGPAT5)

Target: AGPAT5
Molecular classification: Enzyme, Acyltransferase, Integral membrane protein, Phospholipid biosynthesis enzyme

Overview

1-acylglycerol-3-phosphate O-acyltransferase 5 (AGPAT5) is an integral membrane enzyme responsible for catalyzing the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), a key step in de novo phospholipid biosynthesis. AGPAT5 is localized primarily in mitochondria and microsomes, distinguishing it from other AGPAT isoforms. Its highest expression is found in testis and certain brain neurons involved in metabolic sensing (AgRP neurons), where it plays a role in glucose-dependent neuronal activation and glucagon secretion. Dysfunction or loss of AGPAT5 activity has been implicated in rare metabolic diseases, and its broader biological roles continue to be characterized in lipid metabolism and energy regulation.

Other names: 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon1-AGP acyltransferase 51-AGPAT 5LPAAT-epsilonFLJ11210LPAAT-eLPLAT5Lysophosphatidic acid acyltransferase epsilonlysophosphatidic acid acyltransferase, epsilonlysophospholipid acyltransferase 5testicular tissue protein Li 144

Mechanism of action

For future drugs: Inhibition or modulation of AGPAT5 could alter phospholipid biosynthesis and mitochondrial lipid composition, potentially impacting lipid storage diseases, metabolic regulation, or neuronal glucose sensing

Biological functions

Phospholipid biosynthesisLipid metabolismConversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA)Mitochondrial and nuclear membrane phospholipid synthesisRegulation of neuronal glucose sensing

Disease associations

Congenital generalized lipodystrophy (as part of the AGPAT family)Tango2-related metabolic encephalopathy and arrhythmiasPotential roles in hepatic steatosis/neutral lipid storage diseases via lipid pathway regulationDefective hypoglycemia-induced glucagon secretion (neuronal role in mice)

Safety considerations

Because AGPAT5 is involved in essential phospholipid biosynthesis and mitochondrial function, inhibition could disrupt cellular membrane integrity, lipid metabolism, and systemic energy homeostasisPotential risk for metabolic disorders, hepatic steatosis, or neurological effects if not carefully targeted

Interacting drugs

None documented in current search results (no direct inhibitors, agonists, or antagonists currently identified in the literature)

Biomarkers

AGPAT5 mRNA/protein expression in testis, brain (AgRP neurons), and other tissues could serve as a functional biomarkerNot directly linked to patient selection or efficacy monitoring for drugs, based on current evidence

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