Table 1.

Properties of PLA2 subtypes and their biological roles

Family	Number of isozymes	Nomenclature	General names	Distributions	Enzymatic functions	Lipid mobilization	Phenotipic outcomes in knockout (KO) mice	References
cPLA2	6	PLA2G4A	cPLA2α	Ubiquitous	AA-specific PLA2	Production of AA metabolites or PAF	Attenuations of airway inflammation (acute lung injury, bronchial asthma, and plumonary fibrosis), cerebral infarction, neurodegeneration (Alzheimer’s disease), experimental autoimmune encephalomyelitis, collagen-induced arthritis, metabolic syndrome (atherosclerosis, obesity, and hepatic steatosis), and intestinal cancer. Exacerbations of ulcerative colitis, spinal cord injury, stress-induced cardiac hypertrophy, hemorrhage, female infertility, and renal function.	14–24
iPLA2	9	PNPLA1		Epidermal keratinocytes	ω-O-acylceramide transacylase	Production of ω-O-acylceramide for skin barrier formation	Lethal ichthyosis	68
		PNPLA2	iPLA2ζ/ATGL	Ubiquitous (Abundant in adipose tissue and skeletal muscle)	TG lipase	Hydrolysis of TG in lipid droplets for fatty acid β-oxidation	TG accumulation in multiple tissues, Defective lipolysis and alterd energy metabolism, Cardiac dysfunction, Protection from cancer-associated cachexia by preventing fat loss	57, 58, 60
							Impaired phagocytosis of macrophages and resistance to atherosclerosis (macrophage-specific KO)	144
							Hyperglycemia due to impaired insulin secretion (β-cell-specific KO)	145
		PMPLA3	iPLA2ε/ Adiponutrin	Ubiquitous (Abundant in liver and adipose tissue)	TG lipase retinyl-palmitate lipase	Hepatic TG remodeling for neutral lipid accumulation	Perturbed hepatic fatty acid metabolism and TG accumulation under ER stress	146, 147
							Exacerbation of nonalcoholic fatty liver disease (loss-of-function mutation)	64
		PNPLA6	iPLA2δ/NTE	Ubiquitous	Lysophospholipase	Hydrolysis of LPC	Embryonic lethality due to placental defect	48
							Neurodegeneration (neuron-specific KO)	148
		PNPLA7	iPLA2θ/NRE	Ubiquitous	Lysophospholipase	Hydrolysis of LPC	Aberrant hepatic metabolism (unpublished data)
		PNPLA8	iPLA2γ/PLA2G6B	Ubiquitous	PLA1 or PLA2	Membrane (caldiolipin?) remodeling Production of arachidonate metabolites or PUFA-containing lysophospholipids	Skeletal muscular weakness, heart failure, and impaired adaptive thermogenesis due to mitochondorial dysfunction and reduced β-oxidation, Resistant to diet- induced metabolic syndrome, Neurodegeneration, Susceptibility to parasitic infection, Platelet dysfunction	46, 149–153
		PNPLA9	iPLA2β/PLA2G6	Ubiquitous	PLA2	Membrane remodeling Production of AA metabolites or PAF	Male infertility, Impaired glucose-induced insulin secreteion, Neurodegeneration, Aged-related bone loss, Reduction of pancreatic β-cell apoptosis, migration and contraction of vascular cells, and tumorigenesis of ovarian and breast cancers	54, 55, 154–158
PAF-AH	4	PLA2G7	PAFAH/ Lp-PLA2	Plasma	PAF acetylhydrolase, oxidized phospholipid- specific PLA2	Hydrolysis of extracellular PAF, Degradation of oxidized phospholipids in lipoproteins	Protection from atherosclerosis (human mutations)	78
							Resistance to colon tumorigenesis
		PAFAH2	PAFAH2/PLA2G7B	Liver, Kidney	PAF acetylhydrolase, oxidized phospholipid- specific PLA2	Degradation of oxidized phospholipids in cell membranes	Protection from oxidative stress-induced liver damage	74
		PAFAH1B2	PLA2G8A/PAFAH1 α1 subunit	Ubiquitous	PAF acetylhydrolase	Hydrolysis of intracellular PAF	Male infertility due to impaired testicular spermatogenesis, Reduced Aβ production	73, 159, 160
		PAFAH1B3	PLA2G8B/PAFAH1 α2 subunit	Ubiquitous	PAF acetylhydrolase	Hydrolysis of intracellular PAF	Enlargement of ganglionic eminences in Pafah1b2−/−Pafah1b3−/− mice	161
LPLA2	1	PLA2G15	Lysosomal PLA2	Ubiquitous	PLA1 or PLA2	Lysosomal degradation of phospholipids	Abberant accumulation of non-degraded surfactant phospholipids in lysosomes of alveolar macrophages (phospholipidosis), Impaired selection and maturation of iNKT cells, Impaired adaptive T cell immunity against mycobacterium	80–82
PLAAT	5	PLA2G16	HRASLS3/ H-rev 107/ PLAAT3	Adipocytes	PLA1 or PLA2, N-acyl PE acyltransferase	Production of eicosanoids? N-acyl-PE metabolism?	Resistance to diet-induced obesity and metabolic syndrome	84
ABHD	19	ABHD2		Ubiquitous	Hydratase	PC metabolism?	Increase of smooth muscle cell migration and intimal hyperplasia, Pulmonary emphysema in aged mice due to altered surfactant phospholipid metabolism	161, 162
		ABHD3		Ubiquitous	Medium-chain and oxidatively truncated phospholipid-selective PLA1 or PLA2	Hydrolysis of phospholipids with medium-chain fatty acids	Impaired hydrolysis of myristoyl-phospholipids	90
		ABHD4		Ubiquitous	N-acyl-phospholipid- selective PLA1 or PLA2	Hydrolysis of N-acyl-phospholipids	Impaired hydrolysis of N-acyl-PE	91
		ABHD5	CGI-58	Ubiquitous	Catalytically inactive	Acting as a cofactor for PNPLA2- mediated lipolysis	Impaired hydrolysis of TG, Lethal ichthyosis	163, 164
		ABHD6		Ubiquitous	Lysophospholipase or monoacylglycerol lipase	Hydrolysis of lysophospholipids and 2-AG	Impaired hydrolysis of 2-AG for microglia migration, Enhanced adipose browning, Attenuated diet-induced obesity and metabolic syndrome	92, 93, 165
		ABHD12		Ubiquitous	LysoPS lipase	Hydrolysis of LysoPS	Massive accumulation of LysoPS in brain leading to age-dependent increases in microglial activation, auditory and motor defects	96, 97
		ABHD16A		Ubiquitous	PS lipase	Hydrolysis of PS	Lower lysoPS content in the CNS, Reduced body size, Decreased cytokine production by peritoneal macrophages	96
sPLA2	11	PLA2G1B	sPLA2-IB	Pancreatic acinar cells	PLA2	Dietary and biliary phospholipid digestion	Resistance to diet-induced obesity, insulin resistance, and atherosclerosis	105, 106, 108
		PLA2G2A	sPLA2-IIA	Small intestinal Paneth cells, Leukocytes, Platelets, Epithelial cells	PLA2	Degradation of bacterial membrane phospholipids, Hydrolysis of microparticular phospholipids to yield eicosanoids and lysophospholipids	Resistance to bacterial infection (transgenic mice)	113, 114
							Resistance to arthritis	115, 126, 166
							Increased susceptibility to colorectal cancer (natural mutation)	167
		PLA2G2D	sPLA2-IID	Lymphoid DCs	PLA2	Preferential production of ω3 PUFA- derived pro-resolving lipid mediators	Exacervation of contact hypersensitivity and psoriasis, Protection from skin cancer and viral infection	7, 116, 117
		PLA2G2E	sPLA2-IIE	Hypertrophic adipocytes, Hair follicles	PLA2	Hydrolysis of PE and PS in lipoproteins Uncertain	Protection from diet-induced obesity and hyperlipidemia Modest abnormalities in hair follicles	119
								118
		PLA2G2F	sPLA2-IIF	Epidermal keratinocytes	PLA2	Production of lysoplasmalogen	Protection from psoriasis and skin cancer	6
		PLA2G5	sPLA2-V	Hypertrophic adipocytes, Bronchial epithelial cells, Macrophages, Smooth muscle cells, Cardiomyocytes	PLA2	Hydrolysis of PC in LDL to yield OA	Exacerbation of diet-induced obesity and associated metabolic phenotypes	119
						Hydrolysis of lung surfactant	Neonatal death due to a respiratory defect (transgenic mice)	123
							Resistance to LPS-induced airway injury	168
						Production of eicosanoids?	Reduced Th2 response and asthma	124, 131
						Production of LPE or cys-LTs?	Defective phagocytosis of harmful materials leading to increased susceptibility to infection and arthritis	125–127
						Uncertain	Protection from atherosclerosis (hematopoietic cell-specific KO), aortic rupture, and myocardial infarction	169–171
		PLA2G10	sPLA2-X	Colorectal epithelial and goblet cells, Sperm	PLA2	Mobilization of ω3 PUFAs	Exacerbation of colitis and colorectal cancer	24, 167
						Production of eicosanoids and LPC	Attenuation of asthma and influenza-induced pneumonia	130–132
						Hydrolysis of sperm membrane phospholipids to yield DPA and LPC	Reduced male fertility	24, 129
						Production of PGE2?	Reduced insulin secretion	172
						Production of PUFAs that attenuate nuclear receptor signaling?	Hypercorticosteronemia, Reduced TLR4 signaling	173
						Uncertain	Exacerbation of atherosclerosis with increased Th1 immunity (hematopoietic cell-specific KO), Reduced nociception, Attenuation of aneurysm and myocardial infarction	174–176
		PLA2G3	sPLA2-III	Epididymal epithelial cells, Mast cells	PLA2	Sperm membrane phospholipid remodeling	Impaired epididymal sperm maturation and male infertility	135
						Production of microenvironmental PGD2	Impaired mast cell maturation and associated anaphylaxis	136
		PLA2G12B	sPLA2-XIIB	Hepatocytes	Catalytically inactive	Uncertain	Steatohepatitis due to impaired hepatic VLDL secretion	139

Enzymes whose in vivo functions have been analyzed using knockout mice are summarized.