SDHC encodes the membrane-anchoring subunit of succinate dehydrogenase (SDH), the catalytic core of mitochondrial respiratory complex II. SDHC functions to transfer electrons from succinate to ubiquinone (coenzyme Q) during oxidative phosphorylation 1. As a component of complex II, SDHC participates in both the tricarboxylic acid cycle and aerobic respiration, generating the proton gradient essential for ATP synthesis. Germline SDHC mutations cause hereditary pheochromocytoma and paraganglioma syndrome, accounting for approximately 20% of hereditary cases 2. SDHC deficiency represents a tumor suppressor mechanism; loss of SDHC function increases superoxide production from complex II, triggering oxidative stress that promotes both apoptosis and genomic instability leading to malignant transformation 3. Beyond endocrine tumors, SDHC loss promotes metastasis in colorectal cancer by activating PI3K/AKT signaling and reprogramming lipid metabolism, increasing fatty acid synthesis while suppressing oxidation 4. Additionally, SDHC mutations cause SDH-deficient gastrointestinal stromal tumors, a distinct subset representing ~10% of gastric GISTs with unique clinical behavior and therapeutic resistance to imatinib 5. At the molecular level, SDHC deficiency allows accumulation of succinate, which acts as an oncometabolite suppressing DNA repair by inhibiting KDM4B-mediated histone demethylation 6. Genetic testing for SDHC mutations is recommended in all paraganglioma/pheochromocytoma cases, with carriers requiring lifelong biochemical and imaging surveillance 2.