| Claim/Aspect | Key findings | Evidence type | Source (first author, journal) | Year | URL | Citation ID(s) |
|---|---|---|---|---|---|---|
| Identity / synonyms | Human FBXO27 corresponds to FBG5/Fbs3; verified as a lectin-type F-box protein studied in the glycoprotein-recognition literature, matching UniProt Q8NI29 context. | Primary experiment / review | Kumanomidou, *PLoS ONE*; Yoshida, *BioEssays* | 2015; 2018 | https://doi.org/10.1371/journal.pone.0140366 ; https://doi.org/10.1002/bies.201700215 | (pqac-00000005, pqac-00000001) |
| Domains / family | FBXO27 is part of the FBA/lectin-like F-box family; contains the canonical F-box for SKP1 binding plus a conserved glycan-binding G domain that mediates substrate recognition. | Primary experiment | Glenn, *Journal of Biological Chemistry* | 2008 | https://doi.org/10.1074/jbc.m709508200 | (pqac-00000007, pqac-00000006) |
| Glycan specificity | Family-level assays show FBA proteins bind high-mannose and some sulfated glycoproteins; FBXO27 recognizes N-glycans, including high-mannose motifs, and can engage complex-type N-glycans in later work. | Primary experiment / review | Glenn, *Journal of Biological Chemistry*; Yoshida, *BioEssays* | 2008; 2018 | https://doi.org/10.1074/jbc.m709508200 ; https://doi.org/10.1002/bies.201700215 | (pqac-00000008, pqac-00000001, pqac-00000017) |
| SCF complex role | FBXO27 functions as the interchangeable substrate-recognition subunit of an SCF ubiquitin ligase composed of SKP1-CUL1-RBX1 plus FBXO27; all FBA proteins co-precipitated canonical SCF components. | Primary experiment / review | Glenn, *Journal of Biological Chemistry*; Yoshida, *PNAS* | 2008; 2017 | https://doi.org/10.1074/jbc.m709508200 ; https://doi.org/10.1073/pnas.1702615114 | (pqac-00000007, pqac-00000004, pqac-00000029) |
| Lysophagy mechanism | After lysosomal membrane damage (e.g., LLOMe), luminal glycans become exposed to the cytosol; membrane-bound, N-myristoylated FBXO27 is recruited, ubiquitinates exposed lysosomal glycoproteins, and promotes p62/LC3 recruitment for lysophagy. | Primary experiment / review | Yoshida, *PNAS*; Meyer, *Annual Review of Biochemistry* | 2017; 2024 | https://doi.org/10.1073/pnas.1702615114 ; https://doi.org/10.1146/annurev-biochem-030222-102505 | (pqac-00000002, pqac-00000003, pqac-00000016, pqac-00000033) |
| Key substrates | Experimentally supported lysosomal targets include LAMP2 and LAMP1; proteomics also identified other candidate damaged-lysosome glycoproteins such as VAMP3, VAMP7, GNS, PSAP, and TMEM192. LAMP2 is highlighted as especially important for lysophagy initiation. | Primary experiment / review | Yoshida, *PNAS*; Yoshida, *BioEssays* | 2017; 2018 | https://doi.org/10.1073/pnas.1702615114 ; https://doi.org/10.1002/bies.201700215 | (pqac-00000004, pqac-00000012, pqac-00000017) |
| Localization | FBXO27 is membrane-associated rather than purely cytosolic because of N-terminal myristoylation; this membrane targeting is required for efficient recruitment to damaged lysosomes. | Primary experiment | Yoshida, *PNAS* | 2017 | https://doi.org/10.1073/pnas.1702615114 | (pqac-00000002, pqac-00000032) |
| Disease / cancer association | In squamous-cell lung carcinoma datasets, FBXO27 was consistently upregulated across 4 GEO datasets plus TCGA (5 datasets total; 594 tumors, 174 non-tumor tissues). One analysis reported logFC 3.16, FC 8.67, p=3.62E-35, FDR=3.16E-34, though FBXO27 did not remain among the most stringent final DEGs after adjustment. Open Targets shows modest association-level evidence, largely from animal models and one GWAS credible-set record. | Primary expression analysis / database association | Wang, *J Cancer Res Clin Oncol*; Open Targets | 2018; 2025 platform citation | https://doi.org/10.1007/s00432-018-2653-1 ; https://platform.opentargets.org/target/ENSG00000161243 | (pqac-00000025, pqac-00000026, pqac-00000028) |
| Cardiomyocyte autophagy / diabetic cardiomyopathy | 2023 work proposed a CREG1-FBXO27-LAMP2 axis: CREG1 suppresses FBXO27, thereby stabilizing LAMP2 and supporting autophagy in cardiomyocytes. FBXO27 overexpression lowers LAMP2 and impairs autophagy markers; proteasome inhibition increases LAMP2 under pathologic conditions. In vivo, CREG1 deficiency worsened diabetic cardiomyopathy phenotypes, whereas overexpression was protective. | Primary experiment | Liu, *Experimental & Molecular Medicine* | 2023 | https://doi.org/10.1038/s12276-023-01081-2 | (pqac-00000009, pqac-00000010, pqac-00000011) |
| Neuronal lysophagy / high glucose | In high-glucose neuronal models, FBXO27 was evaluated among lysophagy factors. FBXO27 knockdown impaired LGALS3/galectin-3 clearance after lysosomal damage and reduced LysoTracker signal, supporting a role in neuronal lysophagy, although TRIM16 emerged as the dominant regulated factor in that study. | Primary experiment | Chae, *Autophagy* | 2023 | https://doi.org/10.1080/15548627.2023.2229659 | (pqac-00000014, pqac-00000015) |
| Knowledge gaps | Earlier expert review classified many sugar-binding/orphan F-box proteins as lacking well-defined substrates; for FBXO27 specifically, later reviews note partial contribution to total lysosomal ubiquitination, likely cell-type specificity, and unresolved questions about redundancy with ligases such as TRIM16, exact recruitment cues, ubiquitin-linkage logic, and why LAMP2 is favored over LAMP1. | Review / expert analysis | Skaar, *Nature Reviews Molecular Cell Biology*; Meyer, *Annual Review of Biochemistry*; Yoshida, *PNAS* | 2013; 2024; 2017 | https://doi.org/10.1038/nrm3582 ; https://doi.org/10.1146/annurev-biochem-030222-102505 ; https://doi.org/10.1073/pnas.1702615114 | (pqac-00000021, pqac-00000022, pqac-00000024, pqac-00000031, pqac-00000033) |


*Table: This table consolidates the main experimentally supported and review-level findings for human FBXO27/Q8NI29, including identity, molecular function, lysophagy role, and disease relevance. It is useful as a compact evidence map for functional annotation with direct source links and citation IDs.*