| Claim/Aspect | Key findings with quantitative values when available | Primary source (year, journal) plus URL |
|---|---|---|
| Identity | **lbp-8** in *Caenorhabditis elegans* is explicitly mapped to **T22G5.6**: “lbp-8 = T22G5.6”; classified as one of the nematode intracellular fatty acid-binding protein (**iFABP**) genes. Later work identifies LBP-8 as the C. elegans lipid/fatty-acid binding protein studied in longevity signaling. (pqac-00000033, pqac-00000034) | Plenefisch et al. 2000, *Molecular and Biochemical Parasitology*. https://doi.org/10.1016/S0166-6851(99)00179-6; Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8 |
| Family / structure | LBP-8 is an intracellular lipid-binding protein of the **FABP/iLBP** group within the **calycin/lipocalin-like** fold class; the 1.3 Å crystal structure (PDB **6C1Z**) shows the canonical FABP architecture: N-terminal helix-turn-helix lid plus twisted 10-stranded antiparallel β-barrel. Protein is monomeric at ~**16.4 kDa**. The portal region supports a “collisional” FABP-like membrane interaction model. (pqac-00000008, pqac-00000013, pqac-00000018) | Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8 |
| General FABP concept relevant to annotation | FABPs are small cytosolic lipid-binding proteins that act as **sensors, conveyors, and modulators** of hydrophobic metabolites; they typically bind fatty acids noncovalently and can shuttle ligands to membranes or nuclear receptors. These family properties support interpreting LBP-8 as a non-enzymatic lipid chaperone rather than an enzyme. (pqac-00000016, pqac-00000017, pqac-00000020, pqac-00000021) | Agellon 2024, *Journal of Cellular and Molecular Medicine*. https://doi.org/10.1111/jcmm.17703; Zhang et al. 2020, *FEBS Open Bio*. https://doi.org/10.1002/2211-5463.12840 |
| Tissue expression | In the key longevity study, **lbp-8 was exclusively expressed in the intestine**. (pqac-00000014) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857 |
| Subcellular localization | LBP-8 localizes predominantly to **intestinal lysosomes** (co-localization with **LMP-1**) and is also detected in **nuclear and cytoplasmic fractions**; **lipl-4** overexpression enhances nuclear localization. In an LBP-8::GFP strain, **72–100%** of worms showed nuclear enrichment in the first intestinal cell pair under control conditions; **rpc-2 RNAi** significantly reduced nuclear-enriched LBP-8. Visual evidence is in Folick Fig. 1G–I and 2A–G. (pqac-00000000, pqac-00000004, pqac-00000005, pqac-00000030) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Duffy et al. 2021, *bioRxiv*. https://doi.org/10.1101/2021.09.09.459489 |
| Nuclear localization signal | LBP-8 contains an N-terminal / structural **NLS**. Basic residues **K24, R33, K34** form a conserved 3D NLS analogous to mammalian FABP5. Deleting or mutating this region abolishes nuclear translocation, and NLS-deficient LBP-8 loses most longevity activity and fails to induce **acs-2**. (pqac-00000000, pqac-00000003, pqac-00000011) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8 |
| Ligands / binding specificity | LBP-8 binds long-chain fatty acids and fatty-acid derivatives. Reported ligands include **oleoylethanolamide (OEA)**, **oleic acid**, **arachidonic acid (AA)**, **ω-3 AA**, and **DGLA**; competition assays showed **OEA binds with ~3-fold higher affinity** than the tested fatty acids. Structural/lipidomic work indicates preference for **monounsaturated fatty acyls** and identifies co-purifying **palmitic (16:0)** and **oleic (18:1)** acids from *E. coli* and, after exposure to worm extracts, enrichment for **myristic (14:0)** and unsaturated fatty acids including **arachidonic (20:4)**, **linoleic (18:2)**, and **palmitoleic (16:1)**; oleic acid remained most abundant. (pqac-00000002, pqac-00000003, pqac-00000005, pqac-00000009, pqac-00000010) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8 |
| Binding pocket features | The ligand cavity has solvent-accessible surface area ~**825 Ų** and volume ~**1170 ų**; it is lined by hydrophobic residues (**F19, F60, L65, F67, F73, F94, F110, T112, F134**) plus polar residues including conserved **R132** implicated in ligand head-group recognition. Interior/pocket mutants (**Q121A, Y123A, R132A**) altered ligand interactions. (pqac-00000010, pqac-00000012) | Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8 |
| Primary molecular function | Best-supported annotation: LBP-8 is a **non-enzymatic intracellular lipid chaperone** that transfers lysosome-derived lipid signals to the nucleus. It does **not catalyze a reaction**; instead, it binds hydrophobic ligands and facilitates their delivery to transcriptional regulators. (pqac-00000000, pqac-00000018, pqac-00000021, pqac-00000024) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Agellon 2024, *Journal of Cellular and Molecular Medicine*. https://doi.org/10.1111/jcmm.17703 |
| Upstream pathway input | **LIPL-4** lysosomal lipase induction upregulates **lbp-8** and increases nuclear translocation of LBP-8. LIPL-4 overexpression elevates OEA and other fatty acids and extends mean lifespan by about **55%**. LBP-8 is required for much of this effect. (pqac-00000000, pqac-00000005, pqac-00000025) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857 |
| Downstream pathway / nuclear receptors | LBP-8 acts in a **lysosome-to-nucleus lipid signaling** pathway activating nuclear receptors **NHR-49** and **NHR-80**. OEA binds **NHR-80** directly with **Kd = 7.841 µM**; no OEA binding was detected for NHR-49, consistent with NHR-49 acting as a cofactor/partner. LBP-8 nuclear action increases transcription of targets such as **acs-2**; **acs-2** induction exceeded **10-fold** in lbp-8 transgenics but not in NLS-deficient transgenics. (pqac-00000002, pqac-00000005, pqac-00000024, pqac-00000029) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Doering et al. 2023, *Frontiers in Physiology*. https://doi.org/10.3389/fphys.2023.1241591 |
| Nutrient / metabolic regulation | **nhr-49** regulates **lbp-8** expression in nutritional response pathways; earlier work reported **~4-fold** compromised lbp-8 expression in fed **nhr-49(nr2041)** mutants. Review literature in 2023 emphasizes NHR-49 as a central regulator of lipid metabolism, stress resilience, and healthy aging, providing context for LBP-8’s placement in this pathway. (pqac-00000029) | van Gilst et al. 2005, *PNAS*. https://doi.org/10.1073/pnas.0506234102; Doering et al. 2023, *Frontiers in Physiology*. https://doi.org/10.3389/fphys.2023.1241591 |
| Longevity phenotype | **lbp-8 overexpression** increases mean lifespan by about **30%**. **lbp-8 loss-of-function** does not strongly alter WT lifespan but reduces **lipl-4**-mediated lifespan extension by about **46%**. A transgenic LBP-8 lacking the NLS shows little or no lifespan extension. Visual lifespan evidence is in Folick Fig. 2I. (pqac-00000000, pqac-00000005, pqac-00000030) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857 |
| OEA-related quantitative effects | OEA or an OEA analogue increased transcription of **lbp-8** by **>4-fold** and **acs-2** by **>7-fold** after **3 h** treatment; direct OEA-analogue treatment prolonged WT lifespan but did not further extend lifespan in **lipl-4** or **lbp-8** transgenics. **nape-1** loss suppressed lifespan extension in **lipl-4 Tg** and **lbp-8 Tg** by about **half**. (pqac-00000002) | Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857 |
| Additional phenotypic / functional effects | A 2021 proteomic-genetic study reported that LBP-8 overexpression reduced fat storage and upregulated mitochondrial β-oxidation genes; in a screen, day-17 survival averaged **56% alive vs 38% WT** for the overexpression strain under EV controls. (pqac-00000001, pqac-00000004, pqac-00000028) | Duffy et al. 2021, *bioRxiv*. https://doi.org/10.1101/2021.09.09.459489 |
| Protein partners / nuclear retention | Anti-FLAG IP-MS identified **45** candidate LBP-8 interactors (≥**50-fold** enrichment cutoff; replicate correlations **R = 0.89–0.94**). Several genes were required for LBP-8-mediated longevity, especially the nuclear factor **RPC-2**, which was also necessary for robust nuclear localization of LBP-8; nuclear **import**, rather than export, was required for the longevity effect. (pqac-00000001, pqac-00000004, pqac-00000007, pqac-00000028) | Duffy et al. 2021, *bioRxiv*. https://doi.org/10.1101/2021.09.09.459489 |
| Relationship to inter-tissue lipid signaling | In a broader lysosomal lipid-signaling network, **LBP-3** and **LBP-8** can have additive effects on lifespan; **nhr-49** is required downstream of intestine-derived lysosomal lipid signaling to neuropeptide pathways. However, lbp-8 alone had minimal effect on some neuropeptide transcripts compared with lbp-3. (pqac-00000027) | Savini et al. 2022, *Nature Cell Biology*. https://doi.org/10.1038/s41556-022-00926-8 |
| Key methods supporting annotation | Gene-family mapping / sequence inspection; transgenics and mutant analysis; RNAi; lysosome marker co-localization (**LMP-1**); nuclear/cytoplasmic fractionation; lifespan assays; fluorescence competition binding; intrinsic fluorescence for receptor binding; X-ray crystallography (**1.3 Å**, PDB **6C1Z**); 1,8-ANS binding assays; differential scanning fluorimetry; circular dichroism; lipid extraction and mass spectrometry; anti-FLAG IP-MS proteomics. (pqac-00000000, pqac-00000002, pqac-00000004, pqac-00000013, pqac-00000026, pqac-00000030) | Plenefisch et al. 2000, *Molecular and Biochemical Parasitology*. https://doi.org/10.1016/S0166-6851(99)00179-6; Folick et al. 2015, *Science*. https://doi.org/10.1126/science.1258857; Tillman et al. 2019, *Scientific Reports*. https://doi.org/10.1038/s41598-019-46230-8; Duffy et al. 2021, *bioRxiv*. https://doi.org/10.1101/2021.09.09.459489 |


*Table: This table summarizes identity, molecular function, localization, pathway placement, ligands, phenotypes, and methods for C. elegans LBP-8 using only the cited evidence sources. It is useful as a compact evidence matrix for functional annotation of lbp-8/T22G5.6 (UniProt O02324).*