ACSBG2 is an acyl-CoA synthetase that catalyzes the conversion of long-chain and very long-chain fatty acids to their active acyl-CoA forms, supporting both lipid synthesis and beta-oxidation 1. The enzyme demonstrates preferential activation of oleic acid (C18:1ω9) and linoleic acid (C18:2ω6) 1, with activity distributed across diverse saturated, monounsaturated, and polyunsaturated fatty acids. ACSBG2 expression is primarily confined to testis and brainstem, specifically in Sertoli cells and large motoneurons 1, indicating tissue-specific roles in reproductive and neuronal lipid metabolism. Disruption of ACSBG2 is implicated in male infertility pathophysiology. Multi-omics analysis identified ACSBG2 as a key gene dysregulated in non-obstructive azoospermia (NOA), with associated reductions in omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid 2. ACSBG2 is also identified among seven core genes involved in coronary atherosclerosis pathology 3 and appears dysregulated in early Alzheimer's disease cortex, where lipid metabolic dysfunction contributes to pathogenesis 4. These findings suggest ACSBG2 plays important roles in spermatogenesis, vascular homeostasis, and neuronal lipid metabolism, making it a potential biomarker and therapeutic target in reproductive, cardiovascular, and neurodegenerative disorders.