PLSCR3 is a phospholipid scramblase enzyme that catalyzes calcium-induced, ATP-independent bidirectional movement of phospholipids across mitochondrial membranes 1. The protein localizes to mitochondria through palmitoylation at cysteine residues 159-166, which is essential for its mitochondrial targeting and pro-apoptotic function 2. PLSCR3 plays a critical role in apoptosis by facilitating cardiolipin externalization from the inner to outer mitochondrial membrane, enhancing cytochrome c release and amplifying caspase activity 3. The protein is upregulated during heavy metal-induced apoptosis and serves as a mediator connecting mitochondrial dysfunction to cell death pathways 3. PLSCR3 also regulates mitophagy through TGFB1 signaling, promoting cardiolipin externalization in conjunction with autophagy receptor proteins 4. Additionally, PLSCR3 has been identified as the essential biological target for the mitoprotective drug SS-31, with direct binding stimulating its scramblase activity 1. Loss of PLSCR3 function is associated with metabolic dysfunction, including adiposity, insulin resistance, and dyslipidemia, suggesting roles in lipid metabolism and adipocyte function 5. The protein shows tissue-specific expression patterns and has potential clinical relevance as a biomarker in diabetic retinopathy and acute kidney injury 61.