PRELID2 (PRELI domain containing 2) is a mitochondrial protein with phospholipid transfer activity localized to the intermembrane space 1. Functionally, PRELID2 plays a critical role in reactive oxygen species (ROS) generation and is an essential component of oncogenic signaling pathways. In hepatocellular carcinoma, PRELID2 functions downstream of the MEK/ERK/mTOR axis, where its ROS-generating activity is required for tumor progression and metastasis induced by FBXL6/KRAS signaling 1. In gastric cancer, a circular RNA (circPRELID2) promotes epithelial-mesenchymal transition and metastasis under hypoxic conditions by modulating PCBP1 O-GlcNAcylation, which derepresses ZEB2 translation 2. PRELID2 expression is regulated by hypoxia-inducible factor 1-alpha (HIF1A) 2. Beyond cancer, PRELID2 downregulation through miR-486-5p upregulation is implicated in polycystic ovary syndrome pathogenesis and may affect follicular development 3. PRELID2 has emerged as a therapeutic target in pancreatic ductal adenocarcinoma, where PRELID2 siRNA suppresses cell growth more effectively than CA9 inhibition 4. Genetically, PRELID2 variants are associated with cardiovascular disease susceptibility, with SNPs showing significant associations with LDL-cholesterol levels and coronary artery disease risk 5. Additionally, PRELID2 genetic variation influences interferon response in chr5 hepatitis B patients 6.