{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRETREG1 (also known as FAM134B) is a selective receptor for endoplasmic reticulum autophagy (ER‐phagy) that plays a critical role in maintaining ER homeostasis. It mediates the recognition and delivery of ER fragments to autophagosomes by binding to LC3/GABARAP proteins, thereby regulating ER size, turnover, and quality control—including the clearance of misfolded or aggregation‐prone proteins such as aberrant procollagens. Loss‐of‐function mutations in RETREG1 have been linked to sensory and autonomic neuropathies, emphasizing its importance in neuronal survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructurally, RETREG1 possesses a reticulon homology domain (RHD) featuring two wedge‐shaped transmembrane helical hairpins and amphipathic helices that enable it to induce membrane curvature, oligomerize, and facilitate ER membrane fragmentation. Under conditions of ER stress, RETREG1 oligomerization is enhanced by CAMK2B‐mediated phosphorylation, a process that promotes localized ER scission necessary for efficient selective autophagy. In contrast, pathogenic mutations such as G216R disturb this regulation, causing hyperactive self‐association and excessive ER turnover which can trigger neuronal cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in ER maintenance, RETREG1 is implicated in diverse physiological and pathological processes. It participates in the ER quality‐control network by selectively clearing misfolded client proteins, restricts flavivirus infection (whereby viral proteases even target RETREG1 to subvert ER‐phagy), and its expression is upregulated by nutrient‐responsive transcription factors to coordinate cellular responses to metabolic and developmental cues. Dysregulation of RETREG1 activity is associated with neurodegeneration, carcinogenesis, and impaired antiviral responses, underscoring its broad impact on cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ingo Kurth, Torsten Pamminger, J Christopher Hennings, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.464"}], "href": "https://doi.org/10.1038/ng.464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19838196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19838196"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Aliaksandr Khaminets, Theresa Heinrich, Muriel Mari, et al. 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