Acmsd, short for α -amino -β -carboxymuconate -ε -semialdehyde decarboxylase, is a key enzyme in the kynurenine pathway, which is responsible for the catalytic breakdown of tryptophan into NAD+ [3]. It acts as a modulator of de novo NAD+ synthesis from tryptophan, and its expression is largely restricted to the liver and kidney [1,4]. NAD+ is a co -substrate for several enzymes, and the regulation of its synthesis by Acmsd is crucial for various biological processes such as mitochondrial homeostasis and metabolism [4].

In mouse models of metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH), therapeutic inhibition of Acmsd increases liver NAD+ levels, reversing MASLD/MASH by mitigating fibrosis, inflammation, and DNA damage [1]. In diabetic cardiomyopathy mouse models, increased expression of Acmsd leads to impaired de novo NAD+ synthesis in the heart, while inhibition of Acmsd could potentially improve the condition [2].

In conclusion, Acmsd is a vital regulator of de novo NAD+ synthesis. Studies using mouse models have revealed its significance in diseases like MASLD/MASH and diabetic cardiomyopathy. These findings suggest that targeting Acmsd could be a potential therapeutic strategy for these conditions, highlighting the importance of Acmsd in understanding disease mechanisms and developing new treatments.