APOOL (apolipoprotein O-like) is a mitochondrial inner membrane protein that functions as a critical component of the MICOS (mitochondrial contact site and cristae organizing system) complex 1. Located in the intermembrane space, APOOL specifically binds cardiolipin, a signature mitochondrial phospholipid, and physically interacts with core MICOS subunits including Mitofilin, MINOS1, and SAMM50 1. The protein plays a crucial role in maintaining cristae morphology and junctions between inner and outer mitochondrial membranes 2. Functionally, APOOL regulates mitochondrial architecture and respiration; its overexpression causes mitochondrial fragmentation and reduced oxygen consumption, while downregulation impairs respiration and alters cristae structure 1. Beyond its established mitochondrial role, APOOL has emerged as a disease biomarker in multiple cancer types. It appears in prognostic gene signatures for breast cancer, esophageal carcinoma, and glioblastoma, where altered expression correlates with patient survival outcomes 3456. Recent imaging-based analysis identified APOOL perturbation as causing distinct mitochondrial morphological disruptions 7, highlighting its importance in maintaining proper mitochondrial dynamics. These findings establish APOOL as both a fundamental mitochondrial structural protein and a potential therapeutic target in cancer.