ACBD3 (acyl-CoA binding domain containing 3) is a multifunctional scaffolding protein primarily localized to the Golgi apparatus and ER-Golgi contact sites. Its primary function involves organizing membrane trafficking and signaling at the secretory pathway 1. ACBD3 recruits phosphatidylinositol 4-kinase beta (PI4KB) to Golgi and trans-Golgi network membranes, increasing PI4KB enzymatic activity and maintaining essential PI4P pools critical for Golgi function 2. Additionally, ACBD3 acts as an A-kinase anchoring protein, directly interacting with PKA regulatory subunit II at the Golgi to coordinate ER-to-Golgi protein trafficking 3. During viral infections, ACBD3 plays opposing roles depending on the pathogen. For flaviviruses like tick-borne encephalitis virus (TBEV), ACBD3 coordinates ER-Golgi contacts with viral protein NS4B to enable productive infection by facilitating ER remodeling, RNA replication, and virion release 4. In contrast, ACBD3 recruits PI4KB for Aichi virus RNA replication [UniProt annotation]. Clinically, ACBD3 overexpression is associated with poor prognosis across multiple cancers. In breast cancer specifically, elevated ACBD3 correlates with advanced clinicopathological features and reduced relapse-free survival 5, 6. ACBD3 promotes breast cancer stem cell self-renewal through Wnt/β-catenin pathway activation 5, suggesting ACBD3 as a potential therapeutic target 7.