NAXE, also known as APOA1BP, encodes NAD(P)HX epimerase, which is a key enzyme in the NAD(P)HX repair system. This system is responsible for restoring NADH and NADPH after their inactivation by hydration, playing a crucial role in maintaining normal cellular redox cofactor function. The NAD(P)HX repair pathway is essential for preventing metabolic derangements and ensuring proper functioning of biological processes, especially those related to mitochondrial function [1,2].

NAXE deficiency is a rare neurometabolic disorder. Patients with NAXE deficiency present diverse symptoms such as rapidly progressive muscle weakness, ataxia, ophthalmoplegia, motor and cognitive regression, and in some cases, skin manifestations like well-demarcated erythematous and erosive plaques. Stress can trigger decompensation due to the accumulation of NAD(P)HX and depletion of NAD(P)H in the absence of proper repair. Niacin-based therapies show promise in reversing primary metabolomic abnormalities and improving the clinical status of patients [1,2,3,4,5,6].

In conclusion, NAXE is essential for the proper function of the NAD(P)HX repair system, which is crucial for maintaining normal cellular metabolism and mitochondrial function. Studies on NAXE-related neurometabolic disorders have provided insights into the disease mechanisms and potential treatment strategies, highlighting the importance of understanding NAXE function in preventing and treating these rare and often fatal conditions.