NAXD (NAD(P)HX dehydratase) is an ATP-dependent enzyme that catalyzes the dehydration of the S-form of NAD(P)HX, a redox-inactive damaged derivative of the central metabolic cofactors NAD(P)H 1. Working in concert with NAD(P)HX epimerase (NAXE), NAXD repairs both epimers of NAD(P)HX that accumulate from enzymatic or heat-dependent hydration of NAD(P)H 1. NAXD exists as both mitochondrial and cytosolic isoforms generated from alternative start codons; the mitochondrial form is initiated from exon 1 containing a mitochondrial propeptide, while the cytosolic isoform starts in exon 2 1. NAXD deficiency causes progressive, early-onset encephalopathy with brain edema and/or leukoencephalopathy 2 (PEBEL2), an autosomal recessive metabolite repair disorder 2. Disease manifestations depend on affected isoforms: variants affecting both cytosolic and mitochondrial forms present with neurological defects, seizures, and skin lesions triggered by febrile illness 1. Mitochondrial-only variants cause myopathy and cardiac manifestations without neurological degeneration or skin involvement 1. At the molecular level, NAXD deficiency leads to accumulation of damaged NAD(P)HX species, mitochondrial dysfunction, impaired serine synthesis, and NAD+ depletion during metabolic stress 3 4. Niacin and nicotinamide riboside supplementation show therapeutic promise by restoring NAD(P)H metabolism 4.