SERAC1 (serine active site containing 1) is a mitochondrial protein localized at the mitochondria-endoplasmic reticulum interface that performs two critical functions in cellular metabolism. First, SERAC1 facilitates mitochondrial serine transport by stabilizing the serine transporter SFXN1, enabling cytosolic serine import essential for the one-carbon cycle and nucleotide synthesis required for mitochondrial DNA replication 1. Second, SERAC1 mediates phosphatidylglycerol (PG) remodeling by exchanging sn-1 acyl chains from PG 16:0/18:1 to PG 18:0/18:1, maintaining proper mitochondrial membrane composition and intracellular cholesterol trafficking 2. Biallelic SERAC1 mutations cause MEGDEL syndrome (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome), an autosomal recessive mitochondrial disorder affecting the brain, ears, and multiple organs 3. Loss of SERAC1 function impairs nucleotide homeostasis, causing primary mitochondrial DNA depletion and defective oxidative phosphorylation 1. Additionally, disrupted PG remodeling leads to cardiolipin abnormalities and free cholesterol accumulation 2. Over 102 MEGDEL patients have been reported with variable phenotypes and typically poor outcomes, though nucleotide supplementation may offer therapeutic potential 31.