ACSBG1 (acyl-CoA synthetase bubblegum family member 1) is a fatty acid-activating enzyme that catalyzes conversion of long-chain and very long-chain fatty acids to acyl-CoA derivatives, supporting both lipid synthesis and beta-oxidation 123. The enzyme activates diverse saturated, monosaturated, and polyunsaturated fatty acids and is localized to the endoplasmic reticulum, cytoplasm, and plasma membrane 1. In brain lipid metabolism, ACSBG1 is essential for long-chain fatty acid activation during development, with highest expression in the cerebellum and significant expression in tissues affected by X-linked adrenoleukodystrophy (XALD) including brain, adrenal gland, and testis 4. However, ACSBG1 depletion in mice unexpectedly decreased saturated very long-chain fatty acid levels and altered polyunsaturated fatty acid composition, suggesting ACSBG1 is unlikely a direct contributor to XALD pathology 4. Clinically, ACSBG1 exhibits tumor-suppressive functions across multiple cancers. In lung adenocarcinoma, low ACSBG1 expression correlates with advanced tumor stages and poor survival, and ACSBG1 overexpression suppresses proliferation while promoting immune infiltration 5. In glioblastoma, ACSBG1 upregulation in the tumor rim associates with invasive properties 6. Conversely, in obesity-driven breast cancer and esophageal squamous cell carcinoma, ACSBG1 promotes tumor progression, suggesting context-dependent roles in cancer pathogenesis 78.