SCP2 (sterol carrier protein 2) is a lipid transfer protein that mediates transport of lipids between cellular compartments, with primary roles in cholesterol and phospholipid trafficking and fatty acyl-CoA metabolism. 1 Recent evidence demonstrates that SCP2 primarily functions in transporting fatty acyl-CoAs rather than sterols for peroxisomal beta-oxidation and alpha-oxidation of phytanic acid. 1 Additionally, SCP2 mediates cytoplasmic lipid hydroperoxide (LPO) transport to mitochondria, a process implicated in chondrocyte ferroptosis and osteoarthritis progression. 2 In hepatocytes, SCP2 regulates cholesterol metabolism by modulating HMGCR and CYP7A1 expression, influencing bile composition and potentially gallstone formation. 3 SCP2 also plays a role in steroidogenesis by enhancing cholesterol movement to mitochondria and stimulating pregnenolone synthesis. 4 Dysregulation of SCP2 is clinically significant in multiple contexts: ubiquitination and degradation of SCP2 by Siah1 promotes nonalcoholic fatty liver disease (NAFLD) progression, 5 while elevated SCP2 in osteoarthritic cartilage accelerates ferroptosis-mediated chondrocyte damage. 2 These findings establish SCP2 as a critical regulator of lipid homeostasis with implications for metabolic and degenerative diseases.