Acsbg1, also known as "bubblegum" acyl-CoA synthetase, is a key player in lipid metabolism. It facilitates the activation of long-chain fatty acids (LCFAs) and their integration into essential lipid species, supporting processes like membrane formation, myelination, and energy production [4,5]. It is involved in fatty acid metabolism pathways and is important for maintaining lipid homeostasis and proper physiological functions. Genetic models, such as knockout mouse models, have been crucial in studying its functions.

In Treg cells, genetic deletion of Acsbg1 causes mitochondrial dysfunction and dampens other metabolic pathways. Extrinsic supplementation of Acsbg1-deficient Treg cells with oleoyl-CoA restores the Treg metabolic signature, indicating its role as a metabolic checkpoint for tissue Treg cell homeostasis and resolution of lung inflammation [1]. In CD4+ T cells, Acsbg1 deficiency leads to impaired TH17 and in vitro-induced Treg (iTreg) differentiation, highlighting its importance in maintaining immune homeostasis by regulating T cell differentiation [3]. In the context of obesity-driven breast cancer, breast cancer cells in obese animals upregulate Acsbg1 to promote creatine-dependent tumor progression, revealing its role in the crosstalk between adipocytes and cancer cells in the tumor microenvironment [2]. In the mouse brain, an Acsbg1 knockout mouse model showed developmental and compositional changes in fatty acid levels, though it is unlikely that Acsbg1 directly contributes to the pathology of X-linked adrenoleukodystrophy (XALD) [4,5]. In rats with diabetic cardiomyopathy, Acsbg1 was identified as a hub gene associated with fatty acid metabolism and potentially involved in the disease's occurrence and progression through the lysosome [6].

In summary, Acsbg1 is essential for lipid metabolism-related processes. Model-based research, especially KO mouse models, has revealed its roles in immune regulation, cancer progression, and brain lipid metabolism. These findings contribute to understanding the underlying mechanisms of diseases such as lung inflammation, obesity-driven breast cancer, and diabetic cardiomyopathy, providing potential targets for further research and treatment.