EMC2 (UniProt Q15006; synonyms TTC35, KIAA0103) is a 297-amino acid cytoplasmic scaffold protein that serves as the organizational hub of the ER membrane protein complex (EMC), an essential and evolutionarily ancient multi-subunit insertase residing at the endoplasmic reticulum (ER) membrane. EMC2 contains three tetratricopeptide repeat (TPR) motifs arranged in an α-helical solenoid fold and is classified as a peripheral membrane protein — it does not span the lipid bilayer itself but instead anchors to the cytoplasmic face of the ER through extensive interactions with the transmembrane subunits EMC3, EMC5, and the soluble partners EMC8/EMC9. Its primary molecular function is to form the cytoplasmic vestibule that captures client transmembrane domains (TMDs) from the cytosol and channels them to the membrane-embedded insertase subunit EMC3 for energy-independent membrane insertion.
The EMC inserts two major classes of substrates: (1) tail-anchored (TA) proteins with moderately hydrophobic C-terminal TMDs that cannot be engaged by the canonical GET/TRC40 pathway, and (2) the first TMD of multipass membrane proteins (including G protein-coupled receptors) in the correct N-exo/C-cyto topology, enforcing the "positive-inside rule." Through these activities, EMC2 is indirectly required for cholesterol homeostasis (via biogenesis of squalene synthase and SOAT1), GPCR signaling, rhodopsin biosynthesis and photoreceptor survival, voltage-gated ion channel assembly, and ER–mitochondria lipid transfer. EMC2 is a common essential gene in human cells, is ubiquitously expressed across more than 210 cell types, and its complex is conserved across all major eukaryotic lineages since the last eukaryotic common ancestor (LECA). Functionally, the EMC is also coupled to ER-associated degradation (ERAD) quality control and serves as a host dependency factor exploited by flaviviruses for infection.
This report synthesizes evidence from cryo-electron microscopy structural studies, site-directed mutagenesis, reconstituted biochemical assays, CRISPR genetic screens, comparative genomics, and disease genetics to provide a comprehensive functional annotation of human EMC2.
| Property | Value |
|---|---|
| Gene | EMC2 (Ensembl: ENSG00000104412) |
| Chromosomal location | 8q23.1 (chr8:108,443,601–108,551,893, GRCh38, forward strand) |
| Synonyms | TTC35, KIAA0103 |
| UniProt | Q15006 |
| Organism | Homo sapiens |
| Protein family | EMC2 family (IPR039856) |
| Protein length | 297 amino acids |
| Key domains | Three TPR motifs (aa 87–120, 155–188, 192–225); EMC2-like domain (IPR055217); TPR-like helical domain superfamily (IPR011990) |
| Gene essentiality | Common essential gene (DepMap CRISPR screens; Chronos score ~−0.8 to −1.0) |
The gene symbol "EMC2" unambiguously refers to this ER membrane protein complex subunit in humans. The protein was originally identified as KIAA0103 in early cDNA sequencing projects and later named TTC35 based on its TPR repeats, before being renamed EMC2 following the characterization of the EMC complex.
The EMC was first identified in a systematic yeast genetic screen for factors involved in ER protein folding. Wideman (2015) subsequently demonstrated through comprehensive homology searching that the EMC is "truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members" (PMID: 26512320). The EMC was present in the last eukaryote common ancestor (LECA), underscoring its fundamental importance to eukaryotic cell biology.
The human EMC consists of 9–10 subunits with distinct structural and functional roles:
| Subunit | Topology | Key Role |
|---|---|---|
| EMC1 | Type I TM, large lumenal β-propeller | Lumenal client folding; disease-associated |
| EMC2 | Peripheral/cytoplasmic (TPR scaffold) | Cytoplasmic substrate capture and complex organization |
| EMC3 | Multi-TM, YidC/Oxa1-like fold | Core insertase; forms lipid-exposed membrane groove |
| EMC4 | TM | Membrane groove, lipid transfer |
| EMC5/MMGT1 | TM | Hydrophilic vestibule component |
| EMC6 | TM | Gating regulation |
| EMC7 | Type I TM | Lumenal functions |
| EMC8 | Cytoplasmic | Binds EMC2, cytoplasmic subcomplex |
| EMC9 | Cytoplasmic | Binds EMC2, paralog of EMC8 |
| EMC10 | TM | Regulatory, least conserved |
Multiple cryo-EM structures of the full human EMC have been determined, including in lipid nanodiscs at 3.4 Å resolution (PDB: 6WW7; O'Donnell et al., 2020; PMID: 32459176) and in apo and VDAC-bound states (PDB: 8J0N, 8J0O; Li et al., 2024; PMID: 38517390). These structures reveal a tripartite architecture: a large lumenal domain (dominated by EMC1), a transmembrane region containing a lipid-exposed hydrophilic groove (centered on EMC3, which shares structural homology with the YidC/Oxa1 superfamily of membrane protein insertases; PMID: 35850079; PMID: 32910895), and a cytoplasmic domain forming a moderately hydrophobic vestibule for substrate capture (organized by EMC2).
EMC2 is entirely cytoplasmic, classified as a peripheral membrane protein associated with the ER membrane. Its three TPR repeats create a concave α-helical solenoid structure (~20 helices with two short β-strands), as revealed by the 2.2 Å crystal structure of the EMC2–EMC9 subcomplex (PDB: 6Y4L; PMID: 32459176).
The TPR motifs function as protein–protein interaction domains. In the context of the EMC, EMC2 serves as the central organizing hub for the cytoplasmic face of the complex, with experimentally validated interactions:
The cryo-EM and crosslinking studies by O'Donnell et al. (2020) revealed that "EMC's cytosolic domain contains a large, moderately hydrophobic vestibule that can bind a substrate's transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD" (PMID: 32459176). EMC2 forms a substantial portion of this cytoplasmic vestibule.
Pleiner et al. (2023) mapped the substrate path in detail using site-specific crosslinking, showing that client TA proteins are first captured by methionine-rich loops on the cytoplasmic face, then threaded through a hydrophilic vestibule into the membrane. "Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TA proteins. Similarly, this selectivity filter retains the positively charged soluble domains of multipass substrates in the cytosol, thereby ensuring they adopt the correct topology and enforcing the 'positive-inside' rule" (PMID: 37199759).
Site-directed mutagenesis studies (catalogued in UniProt Q15006, largely from O'Donnell et al. 2020) have mapped the functional surfaces of EMC2 at single-residue resolution:
| Functional Surface | Key Residues | Effect of Mutation |
|---|---|---|
| EMC5 binding | 28, 156, 160, 227 | Loss of EMC5 interaction |
| EMC8 binding | 171, 200, 227 | Decreased/abolished EMC8 interaction |
| EMC3 binding | 180, 259 | Decreased EMC3 interaction |
| Substrate TMD capture | 189, 190, 191 | Decreased TA protein TMD binding |
| No effect on TMD binding | 61, 95, 122, 193, 194 | No detectable change |
The substrate-binding residues (189–191) lie in the TPR3 region, and their proximity to the EMC3-contact residue (180) provides molecular evidence that EMC2 bridges substrate capture and membrane insertion at a defined structural junction. The EMC5 and EMC8 binding sites are distributed along the TPR solenoid, consistent with EMC2 serving as a multi-armed scaffold connecting cytoplasmic and membrane subunits.
{{figure:emc2_domain_map.png|caption=EMC2 functional domain map showing TPR repeats (blue), partner binding sites for EMC3/EMC5/EMC8, substrate TMD interaction residues (189-191), and post-translational modifications. Residue-level annotations are derived from UniProt Q15006 mutagenesis data and cryo-EM structural studies (O'Donnell et al. 2020).}}
EMC2 undergoes N-terminal acetylation at Ala2 (after initiator methionine removal) and lysine acetylation at Lys255. Lys255 is located in the C-terminal helix (residues 247–274) near the EMC3-binding residue (259), suggesting potential regulation of the EMC2–EMC3 interface, though this has not been functionally tested. The best-characterized regulatory modification is ubiquitination of unassembled EMC2, which leads to proteasomal degradation and is prevented by WNK1 binding (PMID: 33964204).
A surprising finding from Pleiner et al. (2021) revealed that the kinase WNK1 (with no lysine kinase 1) moonlights as an essential assembly factor for the EMC. WNK1 "uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and directly competes for binding of E3 ubiquitin ligases, permitting assembly" (PMID: 33964204). Without WNK1, free EMC2 is ubiquitinated and degraded by the proteasome. Depletion of WNK1 destabilizes both the EMC and its membrane protein clients. This quality control mechanism ensures that only properly assembled EMC complexes persist, highlighting EMC2's centrality — the entire complex depends on its successful incorporation.
The landmark study by Guna et al. (2018) established the EMC as a bona fide transmembrane domain insertase. They demonstrated that "known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells" (PMID: 29242231). Critically, purified EMC in synthetic liposomes catalyzed the insertion of its substrates, proving direct insertase activity.
The EMC operates in parallel with the GET/TRC40 pathway but handles a distinct substrate class: TA proteins whose TMDs are moderately hydrophobic — too weak for the GET pathway but requiring assistance for membrane insertion. Jung & Zimmermann (2023) used quantitative proteomics to systematically characterize the client spectra of these pathways, confirming that each handles a distinct subset of membrane proteins (PMID: 37762469). Structural comparisons reveal that both EMC and GET insertases share a conserved hydrophilic groove mechanism, suggesting divergent evolution from a common ancestor (PMID: 35850079; PMID: 32910895).
Beyond TA proteins, the EMC plays a critical role in the cotranslational biogenesis of multipass membrane proteins. It mediates the insertion of the first TMD of multipass proteins in the correct N-exo topology (N-terminus in the ER lumen), enforcing the "positive-inside rule" that governs membrane protein topology (PMID: 37199759). Miller-Vedam et al. (2020) resolved cryo-EM structures of both yeast and human EMC that "reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis" (PMID: 33236988).
Page et al. (2024) demonstrated that the EMC physically and genetically interacts with the back of Sec61 (BOS) complex, a component of the multipass translocon. They proposed "a unifying model for coordination between the EMC, the multipass translocon, and Sec61 for the biogenesis of diverse membrane proteins in human cells" (PMID: 38076791). This places EMC2 within a larger biogenesis network where the EMC inserts the first TMD of multipass proteins and then hands off partially inserted substrates to Sec61/BOS for completion.
The most recent work by Stanton et al. (2026) demonstrated that the EMC acts as a chaperone beyond its insertase function, "facilitating the assembly of heterotrimeric voltage-gated calcium channels" at the ER membrane (PMID: 41648177). This extends EMC function beyond simple insertion to include holding and protecting unassembled membrane protein subunits, facilitating their stoichiometric assembly.
Additionally, Li et al. (2024) resolved cryo-EM structures of human EMC in apo and VDAC-bound states, revealing "a specific interaction between VDAC proteins and the EMC at mitochondria-ER contact sites, which is conserved from yeast to humans. Moreover, [they] identified a gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion" (PMID: 38517390). This gating plug may regulate the switch between the EMC's insertase and chaperone modes.
EMC2 localizes to the cytoplasmic face of the endoplasmic reticulum membrane (GO:0072546, EMC complex; GO:0042406, extrinsic component of ER membrane). It is not itself a transmembrane protein but is tethered to the ER membrane through its extensive interactions with the transmembrane EMC subunits (EMC3, EMC5).
Within the cell, the EMC complex is found at:
EMC2 is ubiquitously expressed across human tissues, detected in more than 210 cell types and tissues (Bgee database, ENSG00000104412), consistent with its fundamental role in ER membrane protein biogenesis.
Volkmar et al. (2019) demonstrated that "insertion of the weakly hydrophobic tail-anchor (TA) of SQS into the ER membrane by the EMC ensures sufficient flux through the sterol biosynthetic pathway while biogenesis of polytopic SOAT1 promoted by the EMC provides cells with the ability to store free cholesterol as inert cholesteryl esters" (PMID: 30578317). EMC deficiency causes diminished cell viability under both limiting and excessive extracellular cholesterol, demonstrating that the EMC is a key biogenic determinant of cellular cholesterol tolerance.
EMC subunits are essential for rhodopsin (Rh1) stabilization. Satoh et al. (2015) showed that "dPob/EMC3, EMC1, and EMC8/9, Drosophila homologs of subunits of ER membrane protein complex (EMC), are essential for stabilization of immature Rh1 in an earlier step than that at which another Rh1-specific chaperone (NinaA) acts" (PMID: 25715730). Xiong et al. (2020) confirmed this in mammals: "Conditional knockout of the Emc3 gene in mice led to mislocalization of rhodopsin protein and death of cone and rod photoreceptor cells" (PMID: 31263175). Hiramatsu et al. (2019) further showed that the EMC specifically facilitates insertion of late-synthesized transmembrane helices of Rh1 (PMID: 31553680).
GPCRs, the largest family of human membrane receptors (~800 members), are key EMC clients. The EMC inserts the first TMD of GPCRs in the correct N-exo orientation, which is essential for subsequent folding of the remaining TMDs. Page et al. (2024) showed that characteristics of a GPCR's soluble domain determine its biogenesis pathway, with the EMC, multipass translocon, and Sec61 coordinating (PMID: 38076791).
The EMC, including EMC2/TTC35, was identified as a host dependency factor for flaviviruses. Barrows et al. (2019) showed that "TTC35 and TMEM111, which we previously demonstrated to be required for yellow fever virus (YFV) infection and others subsequently showed were also required by other flaviviruses. These proteins are components of the human endoplasmic reticulum membrane protein complex (EMC)" (PMID: 31273220). Savidis et al. (2016) independently confirmed that "both flaviviruses require the EMC for their early stages of infection" (PMID: 27342126). Bagchi et al. (2022) further showed that EMC4 specifically promotes DENV–endosomal membrane fusion by mediating ER-to-endosome transfer of phosphatidylserine (PMID: 35834589).
STRING network analysis reveals high-confidence interactions between EMC2 and ERAD components DERL2 (Derlin-2, score = 0.904) and UBAC2 (score = 0.847). A chemogenomic screen by Raj et al. (2015) found that "the set of mutants conferring sensitivity to sr7575 was strikingly narrow, affecting components of the endoplasmic reticulum-associated protein degradation (ERAD) stress response and the ER membrane protein complex (EMC). ERAD-deficient mutants were hypersensitive to sr7575 in both S. cerevisiae and A. fumigatus, indicating a conserved mechanism of growth inhibition between yeast and filamentous fungi" (PMID: 26666917). This functional coupling likely reflects the need for coordinated biogenesis (EMC) and quality control (ERAD) of membrane proteins at the ER.
The following model summarizes the role of EMC2 within the EMC insertase complex:
CYTOSOL
│
┌────────────────────┼────────────────────┐
│ │ │
│ Calmodulin ──► release of TA protein │
│ │ │
│ ┌───────────▼───────────┐ │
│ │ EMC2 VESTIBULE │ │
│ │ (TPR solenoid fold) │ │
│ │ │ │
│ │ EMC8/9 ◄──► EMC2 │ │
│ │ (soluble) │ │ │
│ │ │ res │ │
│ │ WNK1 ──► │ 189- │ │
│ │ (assembly │ 191 │ │
│ │ factor) │ (TMD │ │
│ │ │ bind) │ │
│ │ ▼ │ │
│ │ res 180/259 │ │
│ │ (EMC3 contact)│ │
│ └──────────┬───────────┘ │
│ │ │
═════╪═══════════════════╪════════════════════╪═══
│ ER MEMBRANE │ │
│ ▼ │
│ ┌──────────────────┐ │
│ │ EMC3 INSERTASE │ │
│ │ (hydrophilic │ │
│ │ groove, lipid- │◄── EMC1 │
│ │ exposed) │ EMC5 │
│ │ │ EMC4 │
│ │ Selectivity │ EMC6 │
│ │ filter (+charge │ EMC7 │
│ │ repulsion) │ EMC10 │
│ └────────┬─────────┘ │
│ │ │
│ ▼ │
│ Inserted TMD in │
│ correct topology │
│ (N-exo, positive-inside) │
│ │
└────────────────────────────────────────┘
ER LUMEN
Clients: TA proteins (SQS, VAMP7, etc.)
Multipass proteins (GPCRs, rhodopsin, CaV channels)
Coupled pathways:
→ GET/TRC40 (parallel: handles strongly hydrophobic TA TMDs)
→ BOS/Sec61 (sequential: handles downstream TMDs of multipass proteins)
→ ERAD (quality control: degrades misfolded EMC clients)
Substrate selection logic: The EMC vestibule (formed largely by EMC2) captures TMDs from the cytosol. A charge-based selectivity filter at the vestibule entrance uses electrostatic repulsion to reject mitochondrial TA proteins (which have net negative flanking charges) while accepting ER-destined substrates and enforcing the positive-inside topology rule for multipass proteins. After capture, the TMD is handed off through the EMC2–EMC3 interface into a lipid-exposed, lumenally-sealed intramembrane groove in EMC3 for lateral release into the ER membrane.
EMC2 is notably absent from canonical signaling pathway databases (no KEGG or Reactome pathway annotations). This reflects its role as core biogenesis machinery for ER membrane proteins — a "housekeeping" complex that impacts many downstream pathways indirectly:
| Pathway/Process | EMC Role | Key Clients |
|---|---|---|
| Membrane protein insertion | Primary insertase for moderate-hydrophobicity TMDs | TA proteins, first TMD of multipass proteins |
| GET/TRC40 pathway | Parallel, complementary pathway (handles strong TMDs) | TA proteins with high hydrophobicity |
| Sec61/BOS translocon | Sequential cooperator for multipass protein biogenesis | Downstream TMDs of GPCRs |
| Cholesterol biosynthesis | Biogenesis of pathway enzymes | SQS/FDFT1 (TA protein), SOAT1 (polytopic) |
| Phototransduction | Rhodopsin biogenesis | Rhodopsin/Rh1 |
| Ion channel assembly | Chaperone for complex formation | Voltage-gated Ca²⁺ channels |
| ERAD | Functional coupling; quality control of EMC clients | Misfolded membrane proteins |
| ER–mitochondria communication | Lipid transfer at contact sites | VDAC, SLC25A46 |
While no Mendelian disease has been directly attributed to EMC2 mutations (likely reflecting embryonic lethality of homozygous loss, consistent with its essential gene classification), mutations in related EMC subunits cause severe disease:
EMC2 has been identified as a prognostic indicator in several cancer types:
The mechanistic basis for these associations likely reflects EMC2's essential role in membrane protein biogenesis (including iron-handling proteins like SQS/FDFT1) rather than a direct role in ferroptosis signaling, though this remains to be directly demonstrated.
As a flavivirus host dependency factor, the EMC (including EMC2) represents a potential target for antiviral intervention against dengue, Zika, and yellow fever viruses (PMID: 31273220; PMID: 27342126).
| PDB ID | Method | Resolution | Contents | Reference |
|---|---|---|---|---|
| 6Y4L | X-ray | 2.2 Å | EMC2–EMC9 subcomplex | O'Donnell et al. 2020 |
| 6WW7 | Cryo-EM | 3.4 Å | Full human EMC in nanodisc | O'Donnell et al. 2020 |
| 7ADO | Cryo-EM | 3.39 Å | Human EMC | Miller-Vedam et al. 2020 |
| 8J0N | Cryo-EM | 3.47 Å | Human EMC apo state | Li et al. 2024 |
| 8J0O | Cryo-EM | 3.32 Å | Human EMC + VDAC | Li et al. 2024 |
| Study | Key Contribution | PMID |
|---|---|---|
| O'Donnell et al. 2020 | Architecture of human EMC; cytoplasmic vestibule; EMC2–EMC9 crystal structure | 32459176 |
| Miller-Vedam et al. 2020 | Yeast and human EMC structures; dual insertase/chaperone activities | 33236988 |
| Li et al. 2024 | Human EMC apo and VDAC-bound; gating plug mechanism | 38517390 |
| McDowell et al. 2020 | GET insertase structure; structural homology with EMC | 32910895 |
| Study | Key Finding | PMID |
|---|---|---|
| Guna et al. 2018 | EMC is a TA protein insertase for moderate-hydrophobicity TMDs | 29242231 |
| Pleiner et al. 2023 | Charge-based selectivity filter; positive-inside rule enforcement | 37199759 |
| Pleiner et al. 2021 | WNK1 as EMC2 assembly factor | 33964204 |
| Page et al. 2024 | EMC•BOS holocomplex for GPCR biogenesis | 38076791 |
| Volkmar et al. 2019 | EMC required for cholesterol homeostasis via SQS and SOAT1 | 30578317 |
| Stanton et al. 2026 | EMC chaperone activity for Ca²⁺ channel assembly | 41648177 |
| Jung & Zimmermann 2023 | Systematic characterization of EMC client spectrum | 37762469 |
| Study | Key Finding | PMID |
|---|---|---|
| Satoh et al. 2015 | EMC essential for rhodopsin biosynthesis in Drosophila | 25715730 |
| Xiong et al. 2020 | Emc3 knockout causes photoreceptor death in mice | 31263175 |
| Hiramatsu et al. 2019 | EMC facilitates late TMD insertions of Rh1 | 31553680 |
| Barrows et al. 2019 | EMC2/TTC35 is a flavivirus host dependency factor | 31273220 |
| Savidis et al. 2016 | EMC required for ZIKV/DENV infection | 27342126 |
| Wideman 2015 | EMC conserved since LECA | 26512320 |
| Wang et al. 2023 | EMC1 mutations cause neurodevelopmental disease | 37187958 |
| Raj et al. 2015 | EMC and ERAD functional coupling in chemogenomic screen | 26666917 |
| Janer et al. 2016 | SLC25A46–EMC interaction in mitochondrial lipid homeostasis | 27390132 |
No direct substrate-bound structure: No structure of EMC2 bound to a client TMD has been resolved, leaving the precise substrate capture geometry partially inferred from crosslinking and mutagenesis data.
Regulation of EMC2 function is poorly understood: The acetylation at Lys255 near the EMC3-binding interface hints at post-translational regulation, but the responsible enzyme(s) and functional consequences have not been characterized.
Client specificity determinants incompletely defined: While it is known that EMC handles moderate-hydrophobicity TMDs and the GET pathway handles strongly hydrophobic ones, the precise biophysical thresholds and how EMC2's vestibule discriminates substrates remain incompletely defined.
Disease associations are largely correlative: EMC2's appearances in ferroptosis/cancer prognostic gene signatures likely reflect its essential role in membrane protein biogenesis rather than a direct role in ferroptosis. Mechanistic studies are needed.
Gating plug dynamics unresolved: The gating plug inside the EMC hydrophilic vestibule may regulate switching between insertase and chaperone modes, but its regulation and dynamics during substrate engagement have not been captured.
No EMC2-specific Mendelian disease: This likely reflects embryonic lethality of homozygous loss, but hypomorphic alleles or mosaic states have not been systematically searched for.
Characterize Lys255 acetylation: Use acetylation-mimicking (K255Q) and acetylation-dead (K255R) mutants to test whether this modification regulates EMC2–EMC3 binding affinity and insertase activity in reconstituted assays.
Resolve substrate-bound EMC structure: Use cryo-EM with stalled substrates (e.g., dominant-negative TA proteins) to capture the EMC with a client TMD in the vestibule.
Define EMC2-specific client spectrum: Perform TMT-based quantitative proteomics comparing EMC2-depleted versus EMC3-depleted cells to determine whether EMC2 has functions independent of the insertase.
Screen for EMC2 disease variants: Mine ClinVar and gnomAD for rare EMC2 missense variants at functionally critical residues (189–191, 180, 259) and test their effects on EMC assembly and client protein levels.
Test EMC2 in ferroptosis directly: Determine whether EMC2 knockdown sensitizes cells to ferroptosis inducers and whether this is mediated through loss of specific client biogenesis.
Explore antiviral potential: Determine whether partial EMC inhibition can suppress flavivirus replication without lethal cytotoxicity, leveraging residual insertion capacity from the parallel GET pathway.