CHCHD5 (also termed CHTM1) is a mitochondrial protein containing a characteristic coiled-coil-helix-coiled-coil-helix (CHCH) domain stabilized by two disulfide bonds 1. The protein localizes to both mitochondria and cytosol, where it plays critical roles in cellular metabolism and stress response 2. Mechanistically, CHCHD5 regulates mitochondrial function by maintaining oxidative phosphorylation capacity; CHCHD5 deficiency reduces mitochondrial oxygen consumption, ATP levels, and causes oxidative stress 2. Under nutrient deprivation, CHCHD5 promotes cell survival through PKC, CREB, and PGC-1α signaling pathways and supports lipid metabolism 2. The protein negatively regulates apoptosis-inducing factor 1 (AIF1)-mediated cell death by preventing AIF1 translocation from mitochondria, a mechanism antagonized by p38 kinase during metabolic stress 3. In disease contexts, CHCHD5 expression is significantly elevated in breast and colon cancer tissues, where it promotes tumor cell proliferation under nutrient-limiting conditions 2. Additionally, the CHCHD5 polymorphism rs3748024 is associated with systolic blood pressure, BMI, obesity, and triglyceride levels in pediatric populations 4, linking CHCHD5 to cardiometabolic disease risk. These findings establish CHCHD5 as a metabolic regulator with potential therapeutic relevance in cancer and cardiovascular disease.