| Aspect | Key findings | Evidence/notes | Primary citation (include year) |
|---|---|---|---|
| Activity/substrate | LIPL-4 is a lysosomal acid lipase-like enzyme with acid pH-dependent lipase activity; it hydrolyzes triglyceride substrate and is inferred to release free fatty acids from TAGs and cholesteryl esters. | In lipl-4(tm4417) mutants, triglyceride hydrolysis of ^3H-triolein is reduced at pH 4.5 but not pH 7.4; later work frames lysosomal acid lipases as releasing FFAs from TAGs/CEs in the intestine. | Folick et al., 2015 (pqac-00000003, pqac-00000002) |
| Localization | LIPL-4 localizes to lysosomes in intestinal cells; earlier work also reported localization in intestinal cells and seam cells. A signal peptide is required for proper lysosomal targeting and pro-longevity function. | FLAG::LIPL-4 co-localizes with LMP-1 in intestine; removing the signal peptide largely abolishes downstream effects. Review of earlier experiments notes intestinal and seam-cell localization. | Folick et al., 2015; Lapierre et al., 2011 (pqac-00000003, pqac-00000006, pqac-00000013) |
| Regulation | lipl-4 expression/activity is induced by germline loss, DAF-16/FOXO, TOR inhibition, fasting, and other longevity paradigms including IIS reduction. | Germline-less glp-1 animals require lipl-4 for lifespan extension; TOR inhibition increases lipl-4 mRNA and lipase activity; 2022 work reports induction by fasting and in IIS- or germline-deficient mutants. | Lapierre et al., 2011; Savini et al., 2022 (pqac-00000007, pqac-00000006, pqac-00000002) |
| Pathway/mechanism | LIPL-4 initiates lysosome-to-nucleus and intestine-to-neuron lipid signaling that promotes longevity. One arm uses LBP-8 and nuclear receptors NHR-49/NHR-80; another uses LBP-3 plus PUFAs to induce neuronal neuropeptide signaling. LIPL-4 signaling also increases mitochondrial β-oxidation and mtROS/JUN-1 responses. | LIPL-4 upregulates lbp-8, promotes nuclear LBP-8 signaling, and requires NHR-49/NHR-80; separate work shows intestinal LIPL-4→PUFA→LBP-3→neuronal NHR-49/NLP-11 signaling. Developmental Cell study links LIPL-4/LBP-8 to β-oxidation, reduced ETC complex II activity, mtROS, JUN-1, and oxidative stress tolerance. | Folick et al., 2015; Ramachandran et al., 2019; Savini et al., 2022 (pqac-00000003, pqac-00000001, pqac-00000002, pqac-00000008, pqac-00000009) |
| Phenotypes/quantitative effects | Intestinal lipl-4 overexpression is sufficient to extend lifespan substantially and reduce fat storage; lysosomal targeting is important for full effect. | Mean lifespan increase reported as 55% in one primary study; review cites ~24% mean lifespan extension with intestinal overexpression and lean/fewer lipid droplet phenotypes; in 2024 proteomics, lipl-4 Tg lifespan extension is 72% and drops to 48% when lysosomal AMPK signaling is impaired. | Folick et al., 2015; Johnson, 2020 review summarizing primary data; Yu et al., 2024 (pqac-00000003, pqac-00000004, pqac-00000011) |
| Key lipid mediators | Lipids associated with LIPL-4 signaling include oleoylethanolamide (OEA), arachidonic acid, ω-3 arachidonic acid, dihomo-γ-linolenic acid (DGLA), and broader PUFAs. | Folick et al. identified AA, ω-3 AA, DGLA, and OEA as elevated with lipl-4 overexpression; OEA binds LBP-8 with ~3-fold higher affinity than the other tested lipids. Savini et al. identified DGLA/LBP-3 as key fat-to-neuron longevity signals. | Folick et al., 2015; Savini et al., 2022 (pqac-00000003, pqac-00000002, pqac-00000008) |
| Key genetic dependencies | LIPL-4-mediated longevity depends on autophagy genes and transcriptional regulators including DAF-16, PHA-4, LBP-8, NHR-49, NHR-80, LBP-3, neuronal NLP-11, and neuropeptide processing genes; some branches are daf-16-independent downstream of LIPL-4. | Lifespan extension from lipl-4 overexpression is suppressed by bec-1, lgg-1, vps-34, pha-4 RNAi; lbp-8 loss reduces lipl-4 longevity by 46%; nhr-49/nhr-80 are required; intestine-only fat-1 or fat-3 inactivation abolishes lipl-4 Tg longevity; lbp-3 or nlp-11 loss suppresses lipl-4 Tg lifespan extension; egl-21 inactivation abolishes lipl-4 Tg longevity. | Lapierre et al., 2011; Folick et al., 2015; Savini et al., 2022/2021 (pqac-00000006, pqac-00000003, pqac-00000008, pqac-00000009) |


*Table: This table summarizes experimentally supported functional annotation for C. elegans LIPL-4, including its enzymatic activity, localization, regulatory inputs, signaling pathways, lipid mediators, and key genetic dependencies. It is useful as a compact evidence map for interpreting the molecular role of UniProt Q94252.*