| Category | Key findings | Evidence type | Citation id(s) | Publication year | URL |
|---|---|---|---|---|---|
| Protein identity, localization, motifs | Human LMAN2L (VIPL; UniProt Q9H0V9) is a VIP36-like, ER-resident L-type intracellular lectin/cargo-receptor family member. It is largely non-cycling relative to ERGIC-53/LMAN1 and LMAN2/VIP36. Reported cytosolic sorting motifs include KRFY and an additional RKR ER-retention/localization signal; mutation of KR can redirect VIPL to the cell surface. | Reviews/summaries of prior cell biology; mechanistic thesis synthesis | (pqac-00000003, pqac-00000010, pqac-00000011, pqac-00000020) | 2012, 2023, 2024 | https://doi.org/10.1007/978-3-7091-1065-2_7; https://doi.org/10.17863/cam.108565 |
| Glycan binding and mechanistic role | VIPL/LMAN2L has been reported to recognize deglucosylated high-mannose N-glycans, especially Manα1-2Manα1-2Man motifs; binding is stronger at neutral ER-like pH and is Ca2+-dependent. Proposed role: bind native glycoproteins exiting the calnexin/calreticulin cycle, protect them from demannosylation/ERAD, and possibly hand cargo to ERGIC-53 for anterograde transport. siRNA knockdown delayed secretion of two glycoproteins. Some earlier assays failed to detect sugar binding, so this function remains supported but not fully settled. | Binding assays/competition data, knockdown experiments, mechanistic synthesis | (pqac-00000003, pqac-00000010, pqac-00000015, pqac-00000020) | 2012, 2023 | https://doi.org/10.1007/978-3-7091-1065-2_7; https://doi.org/10.17863/cam.108565 |
| 2016 clinical variant | Homozygous c.158G>A (p.R53Q) in a consanguineous Pakistani family co-segregated with severe intellectual disability and infantile epileptic seizures. Studied pedigree included 5 affected and 7 unaffected relatives; all affected were homozygous, unaffected relatives were heterozygous, supporting autosomal recessive inheritance. | Family-based WES, segregation, Sanger validation, homology modeling | (pqac-00000002, pqac-00000024) | 2016 | https://doi.org/10.1136/jmedgenet-2015-103179 |
| 2019 clinical variant | Heterozygous c.1073delT, p.(Phe358Serfs*16) disrupted the C-terminal KRFY ER-retention motif in a family with autosomal dominant intellectual disability and remitting epilepsy. Functional studies in HeLa cells showed mutant LMAN2L shifted from ER/light-membrane fractions to the plasma membrane; immunofluorescence showed a peripheral “shroud” consistent with surface mislocalization. | WES/segregation plus membrane fractionation and immunofluorescence | (pqac-00000001, pqac-00000004, pqac-00000025, pqac-00000027, pqac-00000028) | 2019 | https://doi.org/10.1002/acn3.727 |
| 2023 clinical variant | A Chinese MRT52 proband carried compound heterozygous variants c.256C>T (p.R86C) and c.902del (p.F301Sfs*8), extending LMAN2L disease beyond homozygous cases. Phenotype included global developmental delay, severe ID, seizures beginning at 2 months, hearing loss, and dystonia; seizures occurred about twice monthly despite therapy. | Trio-WES, Sanger confirmation, ACMG classification, case report | (pqac-00000022, pqac-00000023) | 2023 | https://doi.org/10.1097/cm9.0000000000002285 |
| 2024 HCMV/ERAD finding | HCMV pUS2 targets LMAN2L for degradation through the host E3 ligase TRC8. LMAN2L was downregulated as early as 4 h post-infection, rescued by MG132 but not leupeptin, and restored in ΔUS2 infection. This supports a bona fide ER-resident role for LMAN2L and implicates it in host glycoprotein trafficking exploited by virus. | Quantitative proteomics, viral genetics, inhibitor rescue, knockdown | (pqac-00000009, pqac-00000013) | 2024 | https://doi.org/10.1099/jgv.0.001980 |
| 2024 trafficking/client evidence | In LMAN2L-deficient cells, surface ITGA6 was reproducibly reduced; 2023-2024 proteomic work also detected ITGB1 in the LMAN2L interactome, suggesting integrin-related client trafficking. Effect size reported for ITGA6 in the thesis was ~1.5-fold downregulation upon LMAN2L depletion. | Plasma-membrane profiling, CRISPR/siRNA depletion, interactome proteomics | (pqac-00000007, pqac-00000009) | 2023, 2024 | https://doi.org/10.17863/cam.108565; https://doi.org/10.1099/jgv.0.001980 |
| 2024 proteomics interaction screening | A RUSH-based co-IP/MS study identified 87 candidate VIPL-associated proteins/cargos after localization filtering, including ER/Golgi and COPII-related proteins such as SEC23A, SEC23B, and COPB2, plus many cytoskeleton-associated proteins. Authors cautioned that these are candidate interactors/cargos requiring orthogonal validation. | RUSH live-cell trafficking, GFP-nanobody IP, mass spectrometry, imaging | (pqac-00000008, pqac-00000012) | 2024 | No stable journal URL available in retrieved context |


*Table: This table condenses the main experimentally supported findings for human LMAN2L/VIPL, spanning identity, localization, glycan-binding biology, disease variants, and the most relevant 2023-2024 mechanistic studies. It is useful as a quick-reference evidence map linking each claim to specific cited contexts and source URLs.*