{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRetinol dehydrogenase 10 (RDH10) is a key, NAD⁺‐dependent enzyme that catalyzes the oxidation of all‐trans‐retinol to all‐trans‐retinaldehyde—the critical first step in generating all‐trans retinoic acid (RA) required for diverse biological processes. Its reaction kinetics and substrate selectivity have been characterized at the molecular level, and conserved catalytic residues as well as essential cofactor‐binding motifs have been identified, providing insight into its mechanism of action. Moreover, RDH10 partners with the retinaldehyde reductase DHRS3 to form a bifunctional retinoid oxidoreductive complex that mutually activates and stabilizes both components, thereby establishing a robust control over RA biosynthesis during embryogenesis and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental biochemical role, RDH10 expression and activity are tightly regulated across tissues and under varying physiological conditions. In dendritic cells, for instance, a subset expresses RDH10 along with other retinoid‐metabolizing enzymes to generate RA that is critical for modulating immune responses. In metabolic tissues such as liver, pancreas, and kidney, energy status and circulating factors (e.g., insulin via FoxO1 signaling) modulate RDH10 levels, thereby influencing local and systemic RA biosynthesis. In addition, RDH10 is indispensable during embryonic development; mutations or altered expression are associated with craniofacial malformations such as choanal atresia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of RDH10 has increasingly been linked to oncogenesis and tumor progression. In certain cancers—such as non‐small‐cell lung cancer—RDH10 is frequently mutated in advanced tumors, correlating with disease progression. In hepatocellular carcinoma, forced over‐expression of RDH10 produces an antiproliferative effect that echoes the actions of retinoids, while in multiple myeloma its expression pattern has been associated with poorer overall survival. Furthermore, RDH10 appears to promote aggressive characteristics in gliomas, including enhanced migratory and invasive capacities, with evidence indicating that in spinal cord glioma RDH10 facilitates epithelial–mesenchymal transition via activation of the PI3K‐AKT pathway. Preliminary observations in ovarian clear cell carcinoma further implicate altered RDH10 in tumor progression."}, {"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": "P Picozzi, A Marozzi, D Fornasari, et al. 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