VDAC1 is a multifunctional voltage-dependent anion channel embedded in the outer mitochondrial membrane that serves as a central metabolic gatekeeper regulating cellular fate 1. Beyond ion transport, VDAC1 catalyzes phospholipid scrambling across the mitochondrial membrane and regulates critical cellular processes including Ca2+ homeostasis, oxidative stress, and mitochondria-mediated apoptosis by controlling pro-apoptotic protein release 2. The protein interacts with over 100 proteins and oligomerizes to form large channels permitting mitochondrial protein and DNA release 1. VDAC1 participates in endoplasmic reticulum-mitochondrial crosstalk via the IP3R-GRP75-VDAC1 axis, regulating Ca2+ fluxes and mitochondrial bioenergetics 34. Parkin-mediated mono- versus polyubiquitination of VDAC1 differentially regulates mitophagy and apoptosis, with monoubiquitination promoting apoptosis through enhanced mitochondrial Ca2+ uptake 5. VDAC1 overexpression is elevated in Alzheimer's disease brains and contributes to neuronal cell death 2. Additionally, VDAC1 regulates ferroptosis resistance in cancer cells through prevention of oligomerization 6. These diverse functions establish VDAC1 as a druggable target for treating neurodegenerative diseases, cancer, diabetes complications, and ischemic injury 17.