PLEKHN1 (pleckstrin homology domain containing N1) is a multifunctional protein with roles in mitochondrial apoptosis, lipid binding, and cellular stress responses. The protein promotes apoptosis by enhancing BAX-BAK hetero-oligomerization through interaction with BID in colon cancer cells, serving as a pro-apoptotic regulator during reactive oxygen species-induced cell death 1. PLEKHN1 binds to multiple phospholipids including cardiolipin, phosphatidic acid, phosphatidylinositol 4-phosphate, and phosphatidylserine, and localizes to mitochondrial membranes 1. The protein exists in both nuclear and vesicular compartments and can interact with bacterial effector proteins, suggesting involvement in host-pathogen interactions 2. PLEKHN1 expression is regulated by hypoxia and appears to be silenced in cancer tissues, potentially contributing to drug resistance acquisition in cancer cells 1. In diabetic cardiomyopathy, PLEKHN1 is among the differentially expressed proteins in early disease stages 3. The gene shows differential methylation patterns across breast cancer subtypes, particularly in the 1p36 chr1 region 4. PLEKHN1 has also been identified as a prognostic biomarker in clear cell renal cell carcinoma, where it influences immune cell populations and patient outcomes 5.