{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNAXE, formerly known as APOA1BP or AIBP, encodes a highly conserved NAD(P)HX epimerase that plays an essential role in cellular metabolite repair by catalyzing the interconversion of damaged NAD(P)H hydrates. This epimerization prevents the accumulation of toxic by‐products that can impair mitochondrial function and disturb cellular redox balance. In humans, biallelic mutations in NAXE lead to severe neurometabolic disorders characterized by acute‐onset encephalopathy, cerebellar edema, leukoencephalopathy, and rapid neurological deterioration—often triggered by febrile illnesses—with outcomes ranging from progressive disability to early childhood lethality."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in NAD(P)HX repair, NAXE (as AIBP) participates in diverse cellular processes that extend its impact on overall cell physiology. By promoting cholesterol efflux from endothelial cells, it modulates membrane lipid raft integrity and attenuates pro‐angiogenic signaling—such as by interfering with VEGFR2 dimerization—thereby serving as a non–cell-autonomous regulator of angiogenesis. Furthermore, NAXE contributes to the regulation of inflammatory responses and even influences mitotic processes by interacting with key proteins and membrane lipids, which has downstream consequences for cell cycle progression and the maintenance of centrosomal structures. Notably, reduced NAXE expression has been linked to pathological states including tumor progression—via increased reactive oxygen species and epithelial–mesenchymal transition—and vascular anomalies such as infantile hemangioma, where impaired NAXE function is associated with aberrant angiogenesis and hypoxia-inducible factor 1α signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ronen Spiegel, Avraham Shaag, Stavit Shalev, et al. 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