LIPE

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004771 sterol ester esterase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Sterol ester esterase activity is supported as a secondary neutral-ester substrate activity rather than the central adipocyte DAG-lipase role. Reason: sterol ester esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. PMID:15716583 Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis.
GO:0004806 triacylglycerol lipase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Triacylglycerol lipase activity is biochemically supported, but HSL is positioned primarily as the DAG lipase downstream of ATGL in stimulated lipolysis. Reason: triacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: The cytosol annotation is consistent with basal HSL localization before stimulated lipid-droplet recruitment. Reason: cytosol is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0019433 triglyceride catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: HSL acts within the canonical triglyceride catabolic cascade by hydrolyzing DAG produced from TAG. Reason: triglyceride catabolic process is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0042572 retinol metabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Retinol metabolism is supported by recent physiology but is a tissue/context-specific secondary role rather than the primary neutral-lipid lipolysis function. Reason: retinol metabolic process is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In 2024, adipocyte HSL was shown to be required for maintenance of circulating retinol and RBP4 during fasting, establishing a concrete systemic vitamin A role.
GO:0004771 sterol ester esterase activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Sterol ester esterase activity is supported as a secondary neutral-ester substrate activity rather than the central adipocyte DAG-lipase role. Reason: sterol ester esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. PMID:15716583 Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis.
GO:0004806 triacylglycerol lipase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Triacylglycerol lipase activity is biochemically supported, but HSL is positioned primarily as the DAG lipase downstream of ATGL in stimulated lipolysis. Reason: triacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0005811 lipid droplet	IEA GO_REF:0000044	ACCEPT	Summary: The lipid droplet annotation captures the regulated site where HSL gains access to stored neutral lipid substrates. Reason: lipid droplet is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: The cytosol annotation is consistent with basal HSL localization before stimulated lipid-droplet recruitment. Reason: cytosol is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plasma membrane association has experimental support through PTRF/caveola studies, but it is not the main functional location of HSL. Reason: plasma membrane is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: PMID:17026959 In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0005901 caveola	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Caveola association is supported in adipocytes through PTRF, but it is secondary to cytosol-to-lipid-droplet recruitment during lipolysis. Reason: caveola is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: PMID:17026959 In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	MODIFY	Summary: The generic lipid metabolic process annotation is directionally correct but too broad for HSL. Lipid catabolic process, and more specifically diacylglycerol catabolic process, better capture the reviewed function. Reason: lipid metabolic process is less informative than the reviewed LIPE/HSL lipolysis term. Proposed replacements: lipid catabolic process Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0008202 steroid metabolic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Steroid metabolic process is plausible through cholesteryl ester hydrolysis in steroidogenic tissues but is not the central LIPE function. Reason: steroid metabolic process is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: PMID:15716583 Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis.
GO:0008203 cholesterol metabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Cholesterol metabolism is supported through cholesteryl ester hydrolysis, but this is a secondary substrate context. Reason: cholesterol metabolic process is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: PMID:15716583 The relatively higher turnover of HSL on CO observed in vitro adds further molecular insight on the physiological importance of HSL in cholesteryl ester catabolism in vivo.
GO:0016042 lipid catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Lipid catabolic process is supported because LIPE/HSL hydrolyzes neutral lipid esters during lipolysis. Reason: lipid catabolic process is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0016298 lipase activity	IEA GO_REF:0000002	MODIFY	Summary: Generic lipase activity should be refined to diacylglycerol lipase activity because DAG hydrolysis is the best-supported core catalytic step. Reason: lipase activity is less informative than the reviewed LIPE/HSL lipolysis term. Proposed replacements: diacylglycerol lipase activity Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0016787 hydrolase activity	IEA GO_REF:0000120	MODIFY	Summary: Generic hydrolase activity obscures the specific serine-lipase reaction supported for LIPE/HSL. Reason: hydrolase activity is less informative than the reviewed LIPE/HSL lipolysis term. Proposed replacements: diacylglycerol lipase activity Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0047372 monoacylglycerol lipase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Monoacylglycerol lipase activity is consistent with broad HSL substrate specificity, but the dominant physiological lipolysis role is DAG hydrolysis. Reason: monoacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0047376 all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Retinyl-palmitate hydrolase activity is supported as part of retinoid mobilization but should be treated as a secondary substrate-specific function. Reason: all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In 2024, adipocyte HSL was shown to be required for maintenance of circulating retinol and RBP4 during fasting, establishing a concrete systemic vitamin A role. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0050253 retinyl-palmitate esterase activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Retinyl-palmitate esterase activity is supported as part of retinoid mobilization but is secondary to the primary DAG lipase role. Reason: retinyl-palmitate esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In 2024, adipocyte HSL was shown to be required for maintenance of circulating retinol and RBP4 during fasting, establishing a concrete systemic vitamin A role. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0120516 diacylglycerol lipase activity	IEA GO_REF:0000120	ACCEPT	Summary: Diacylglycerol lipase activity is the best-supported core molecular function of HSL. Reason: diacylglycerol lipase activity is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic for curation of LIPE; the reviewed biology is better represented by regulated localization to PLIN1-coated lipid droplets and specific lipid hydrolase activities. Reason: protein binding overstates or obscures the specific supported LIPE function. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: The cytosol annotation is consistent with basal HSL localization before stimulated lipid-droplet recruitment. Reason: cytosol is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0019433 triglyceride catabolic process	IEA GO_REF:0000041	ACCEPT	Summary: HSL acts within the canonical triglyceride catabolic cascade by hydrolyzing DAG produced from TAG. Reason: triglyceride catabolic process is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0004771 sterol ester esterase activity	IDA PMID:15716583 Continuous monitoring of cholesterol oleate hydrolysis by ho...	KEEP AS NON CORE	Summary: Sterol ester esterase activity is supported as a secondary neutral-ester substrate activity rather than the central adipocyte DAG-lipase role. Reason: sterol ester esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. PMID:15716583 Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis.
GO:0004771 sterol ester esterase activity	IDA PMID:8812477 Molecular cloning, genomic organization, and expression of a...	KEEP AS NON CORE	Summary: Sterol ester esterase activity is supported as a secondary neutral-ester substrate activity rather than the central adipocyte DAG-lipase role. Reason: sterol ester esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. PMID:15716583 Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis.
GO:0004806 triacylglycerol lipase activity	IDA PMID:15716583 Continuous monitoring of cholesterol oleate hydrolysis by ho...	KEEP AS NON CORE	Summary: Triacylglycerol lipase activity is biochemically supported, but HSL is positioned primarily as the DAG lipase downstream of ATGL in stimulated lipolysis. Reason: triacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0004806 triacylglycerol lipase activity	IDA PMID:15955102 Identification of a novel keratinocyte retinyl ester hydrola...	KEEP AS NON CORE	Summary: Triacylglycerol lipase activity is biochemically supported, but HSL is positioned primarily as the DAG lipase downstream of ATGL in stimulated lipolysis. Reason: triacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase. file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0016020 membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Generic membrane association is retained as non-core because HSL can associate with caveolae and lipid droplets while remaining primarily a regulated soluble lipase. Reason: membrane is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: PMID:17026959 In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0046340 diacylglycerol catabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Diacylglycerol catabolic process is the most precise biological-process annotation for HSL in the lipolysis cascade. Reason: diacylglycerol catabolic process is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids.
GO:0046485 ether lipid metabolic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Ether lipid metabolic process is not supported by the reviewed LIPE literature; the evidence supports neutral acylglycerol, sterol ester, and retinyl ester hydrolysis instead. Reason: ether lipid metabolic process overstates or obscures the specific supported LIPE function. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0047372 monoacylglycerol lipase activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Monoacylglycerol lipase activity is consistent with broad HSL substrate specificity, but the dominant physiological lipolysis role is DAG hydrolysis. Reason: monoacylglycerol lipase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0050253 retinyl-palmitate esterase activity	IDA PMID:15955102 Identification of a novel keratinocyte retinyl ester hydrola...	KEEP AS NON CORE	Summary: Retinyl-palmitate esterase activity is supported as part of retinoid mobilization but is secondary to the primary DAG lipase role. Reason: retinyl-palmitate esterase activity is supported, but it is secondary to the core DAG-lipase role. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In 2024, adipocyte HSL was shown to be required for maintenance of circulating retinol and RBP4 during fasting, establishing a concrete systemic vitamin A role. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0120516 diacylglycerol lipase activity	ISS GO_REF:0000024	ACCEPT	Summary: Diacylglycerol lipase activity is the best-supported core molecular function of HSL. Reason: diacylglycerol lipase activity is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0120516 diacylglycerol lipase activity	IDA PMID:19800417 In vitro stereoselective hydrolysis of diacylglycerols by ho...	ACCEPT	Summary: Diacylglycerol lipase activity is the best-supported core molecular function of HSL. Reason: diacylglycerol lipase activity is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0120516 diacylglycerol lipase activity	IDA PMID:8812477 Molecular cloning, genomic organization, and expression of a...	ACCEPT	Summary: Diacylglycerol lipase activity is the best-supported core molecular function of HSL. Reason: diacylglycerol lipase activity is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0005811 lipid droplet	ISS GO_REF:0000024	ACCEPT	Summary: The lipid droplet annotation captures the regulated site where HSL gains access to stored neutral lipid substrates. Reason: lipid droplet is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0016042 lipid catabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Lipid catabolic process is supported because LIPE/HSL hydrolyzes neutral lipid esters during lipolysis. Reason: lipid catabolic process is supported as part of LIPE/HSL core lipid-droplet lipolysis. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md In the canonical LD lipolysis cascade, ATGL (PNPLA2) initiates triacylglycerol (TAG) breakdown to diacylglycerol (DAG), HSL (LIPE) then preferentially hydrolyzes DAG→monoacylglycerol (MAG) + free fatty acid, and MAG is further hydrolyzed by MAGL to glycerol and fatty acids. file:human/LIPE/LIPE-deep-research-falcon.md HSL has broad substrate specificity, with reported activity against TAG, DAG, MAG, cholesteryl esters, retinyl esters, and other esters; multiple sources emphasize that activity toward DAG is markedly higher than toward TAG, positioning HSL as the dominant DAG lipase in stimulated lipolysis rather than the initiating TAG lipase.
GO:0005515 protein binding	IPI PMID:17026959 Association and insulin regulated translocation of hormone-s...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic for curation of LIPE; the reviewed biology is better represented by regulated localization to PLIN1-coated lipid droplets and specific lipid hydrolase activities. Reason: protein binding overstates or obscures the specific supported LIPE function. Supporting Evidence: file:human/LIPE/LIPE-deep-research-falcon.md HSL is largely cytosolic basally and relocates to the lipid-droplet (LD) surface during stimulated lipolysis, where it interacts functionally with PLIN1-coated droplets. LD recruitment is a major regulatory step controlling substrate access.
GO:0006468 protein phosphorylation	TAS PMID:3420405 Hormone-sensitive lipase: sequence, expression, and chromoso...	REMOVE	Summary: This annotation treats LIPE as if it performs protein phosphorylation. The cited biology describes HSL as a phosphorylation-regulated lipase, not a kinase. Reason: LIPE is regulated by phosphorylation but does not catalyze protein phosphorylation. Supporting Evidence: PMID:3420405 Hormone-sensitive lipase, a key enzyme in fatty acid mobilization, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled through reversible phosphorylation by catecholamines and insulin.

Gene Description

Existing Annotations Review

Core Functions

Cytosol-to-lipid-droplet diacylglycerol lipase activity during hormonally stimulated neutral-lipid mobilization.

References

Deep Research

Falcon

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