{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EMC4 is an integral subunit of the endoplasmic reticulum (ER) membrane protein complex that serves multiple, context‐dependent roles in cellular homeostasis. In the setting of viral infection, EMC4 functions as a molecular tether that, together with other EMC subunits (e.g., EMC7), promotes the targeting of pathogens. For instance, during polyomavirus SV40 infection, EMC4 engages LE‐associated Rab7 and the ER fusion component syntaxin18 to stabilize contacts between late endosomes and the ER, thereby facilitating the virus’s transport and subsequent cytosolic entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, EMC4 is critical for the efficient infection by flaviviruses; its loss impairs viral uncoating and the biogenesis of viral proteins, resulting in markedly reduced infection by dengue, yellow fever, and Zika viruses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n EMC4 also plays an important role in maintaining protein homeostasis and the cellular stress response. In yeast, the Emc4p homolog is necessary for proper eIF2B-mediated translational regulation under stress conditions, with its expression capable of rescuing growth defects associated with eIF2B mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, recent transcriptomic analyses have identified reduced EMC4 expression as a biomarker in neuropathic pain, indicating that its proper expression supports normal neural function and may protect against pathologic pain states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings support a model in which EMC4 functions as a versatile molecular chaperone and tether. By promoting the correct folding, stabilization, and trafficking of membrane proteins, EMC4 helps ensure the integrity of key cellular processes—ranging from viral entry and replication to stress-related translational control and neuronal integrity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Parikshit Bagchi, Mauricio Torres, Ling Qi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Dual roles for the ER membrane protein complex in flavivirus infection: viral entry and protein biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-45910-9"}], "href": "https://doi.org/10.1038/s41598-019-45910-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31273220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31273220"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sonum Sharma, Anuradha Sourirajan, David J Baumler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Saccharomyces cerevisiae ER membrane protein complex subunit 4 (EMC4) plays a crucial role in eIF2B-mediated translation regulation and survival under stress conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Genet Eng Biotechnol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s43141-020-00029-7"}], "href": "https://doi.org/10.1186/s43141-020-00029-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32476094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32476094"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sonum Sharma, Anuradha Sourirajan, Kamal Dev "}, {"type": "b", "children": [{"type": "t", "text": "Role of Saccharomyces cerevisiae TAN1 (tRNA acetyltransferase) in eukaryotic initiation factor 2B (eIF2B)-mediated translation control and stress response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "3 Biotech (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13205-017-0857-8"}], "href": "https://doi.org/10.1007/s13205-017-0857-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28677085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28677085"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jie Bai, Bin Geng, Xingwen Wang, et al. 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