NAXE, also known as APOA1BP, encodes NAD(P)HX epimerase, an enzyme crucial in the NAD(P)HX repair system. This system restores NADH and NADPH after their inactivation by hydration. The repair process is vital for maintaining the redox balance and energy metabolism, as it ensures the proper function of the mitochondrial respiratory chain [1,2].

NAXE deficiency leads to a fatal neurometabolic disorder. Clinical features include rapidly progressive muscle weakness, ataxia, ophthalmoplegia, and motor and cognitive regression [1]. Skin manifestations like well-demarcated erythematous and erosive plaques progressing to blistering and necrosis, mainly affecting flexural surfaces, can also occur [4]. Disease onset is often triggered by fever or infections, and mortality rate is high (78%) [4]. Niacin-based therapies show promise in improving clinical status, reversing primary metabolomic abnormalities, and enhancing survival rates [1,3,4].

In conclusion, NAXE plays an essential role in maintaining the integrity of the NAD(P)H cofactors through the NAD(P)HX repair system. Research on NAXE-related neurometabolic disorders has revealed the potential of metabolic correction therapies. Understanding NAXE's function can provide insights into the underlying mechanisms of these disorders, potentially leading to the development of more targeted treatments.