{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC35C1 encodes a GDP‐fucose transporter localized to the Golgi apparatus that is essential for the proper fucosylation of glycans. Proper fucosylation is required for the formation of selectin ligands on leukocytes, and mutations in SLC35C1 lead to leukocyte adhesion deficiency type II (LAD‐II), a congenital disorder of glycosylation characterized by immunodeficiency, recurrent infections, and developmental abnormalities. In patients with LAD‐II, distinct mutations, including missense changes and truncations, impair the transport activity and/or Golgi localization of SLC35C1, leading to deficient fucosylation of cell surface and secreted glycoproteins. Moreover, supplementation with exogenous fucose can restore fucosylation in cells expressing certain mutant forms of SLC35C1, providing a rationale for fucose‐based therapeutic interventions in affected individuals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in immunodeficiency disorders, SLC35C1 has been implicated in the modulation of cellular signaling in oncogenesis. Altered fucosylation patterns—resulting from aberrant expression of GDP‐fucose transporters including SLC35C1—have been associated with the progression of various cancers. For example, increased fucosylation in hepatocellular carcinoma and enhanced activity of the Wnt signaling pathway in colorectal cancer have been linked, respectively, to the upregulation of fucosylation-related enzymes and the downregulation of SLC35C1, suggesting that loss of proper GDP-fucose transport not only compromises cell adhesion but may also deregulate signaling pathways driving tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed structure–function analyses have further delineated the molecular requirements for SLC35C1 activity. These studies indicate that while the C-terminal domain is dispensable for Golgi localization, it is critical for transporter function through specific motifs, such as clusters of lysine residues and conserved glycine positions. Moreover, comparative in vivo analyses with the related transporter SLC35C2 have underscored the unique role of SLC35C1 in glycoprotein fucosylation and developmental signaling, including pathways like Notch, reinforcing its non-redundant function in normal cellular physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Edith van de Vijver, Anne Maddalena, Özden Sanal, et al. 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