Acads, short-chain acyl-CoA dehydrogenase gene, encodes an enzyme functioning in the mitochondrial β-oxidation of saturated short-chain fatty acids, playing a vital role in free fatty acid β-oxidation and regulating energy homeostasis [4]. It is also associated with pathways like lipid metabolism, ketone metabolism, and is of overall biological importance. Genetic models, such as cell lines with modified Acads expression, are valuable for studying its functions [6].

In hepatocellular carcinomas (HCC), Acads was significantly downregulated, and its loss-of-function was involved in the proliferation and metastasis of HCC. DNA methylation played a key role in regulating Acads expression, and it could be a potential therapeutic target for treating HCC [1].

In an unselected adult population, clinically relevant Acads variants were not associated with evidence of metabolic disease, suggesting that short-chain acyl CoA dehydrogenase deficiency (SCADD) caused by Acads variants might be more of a biochemical entity without clinical correlate, especially when caused by common variants [2].

In chronic obstructive pulmonary disease (COPD), certain Acads gene polymorphisms were associated with increased COPD risk, and some haplotypes were protective, indicating Acads could be a risk factor for COPD [3]. Depletion of Acads significantly inhibited HCC proliferation and metastasis, with calcium signaling pathway activation and intracellular calcium homeostasis dysregulation [5].

In conclusion, Acads is essential in fatty acid and energy metabolism. Studies using different models have revealed its significance in diseases like HCC, metabolic diseases, and COPD. Understanding Acads through these models provides insights into disease mechanisms, potentially guiding future therapeutic strategies for related conditions.