{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSELENOK is a selenium‐containing transmembrane protein resident in the endoplasmic reticulum that plays a pivotal role in modulating intracellular Ca²⁺ dynamics and orchestrating immune responses. Studies in animal models have shown that SELENOK supports receptor‐mediated Ca²⁺ flux in T cells, neutrophils, and macrophages—processes essential for cell proliferation, migration, and pathogen clearance—and also regulates the palmitoylation of IP₃ receptors via interactions with the DHHC6 enzyme. In addition, SELENOK facilitates innate immunity by promoting the oligomerization and ER‐to‐Golgi translocation of the stimulator of interferon gene (STING) during viral infection."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in Ca²⁺ signaling, SELENOK is intricately involved in maintaining ER homeostasis and protein quality control. It forms complexes with components of the ER‐associated degradation (ERAD) machinery (including Derlin-1 and SelS) to mediate the clearance of misfolded glycoproteins. Moreover, SELENOK displays selective peroxidase activity toward phospholipid hydroperoxides, contributing to antioxidant defense and the regulation of cellular redox balance. Its expression is also modulated during metabolic processes; for instance, during adipocyte differentiation, SELENOK is targeted for ubiquitination by PPARγ. In parallel, quality control of selenoproteins may involve recognition of C‐end degron motifs by specific ubiquitin ligases, placing SELENOK within a broader regulatory network."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSELENOK’s roles extend into diverse pathophysiological contexts. In cancer cells, overexpression of SELENOK alters intracellular Ca²⁺ levels leading to decreased cell adhesion and migration as well as increased apoptosis; conversely, its expression is also regulated by microRNAs in hepatocellular carcinoma, highlighting its potential as a modulator of tumor progression. Structural studies reveal that the intrinsically disordered C-terminal domain of SELENOK serves as a hub for multiple protein-protein interactions, which may influence cell signaling and stress responses. In models of tissue degeneration and neurodegenerative disease, upregulation of SELENOK via selenium supplementation has been shown to alleviate mechanical overload–induced ferroptosis in nucleus pulposus cells and enhance microglial clearance of amyloid-β through modulation of CD36 palmitoylation. However, elevated SELENOK levels have also been associated with aggressive behavior in glioblastoma, underscoring its complex role in disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Saguna Verma, FuKun W Hoffmann, Mukesh Kumar, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Selenoprotein K modulate intracellular free Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " by regulating expression of calcium homoeostasis endoplasmic reticulum protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.01.117"}], "href": "https://doi.org/10.1016/j.bbrc.2017.01.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28130108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28130108"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lin Lv, Li Chai, Jie Wang, et al. 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