SDHB encodes the iron-sulfur subunit of succinate dehydrogenase (SDH), a mitochondrial respiratory chain complex II enzyme responsible for transferring electrons from succinate to ubiquinone during aerobic respiration 12. This catalytic function is essential for both oxidative phosphorylation and the tricarboxylic acid cycle. Pathogenic SDHB variants cause loss of SDH function, leading to succinate accumulation and pseudohypoxia, activating hypoxia signaling pathways that promote tumor growth and metastasis 3. SDHB mutations are the most frequent genetic cause of inherited pheochromocytomas and paragangliomas (PPGLs), with cumulative tumor penetrance of approximately 24% by age 60 in carriers 4. SDHB-associated tumors are notably aggressive, with higher rates of metastasis, malignancy, and dopamine-only secretion compared to other hereditary subtypes, enabling subclinical growth 35. Loss of SDHB immunoreactivity predicts metastatic disease in PPGLs 6. Additionally, SDHB mutations cause succinate dehydrogenase-deficient gastrointestinal stromal tumors (approximately 10% of gastric GISTs) that are resistant to standard imatinib therapy 7. Loss of SDHB methylation and elevated expression correlates with recurrent spontaneous abortion risk through dysregulation of trophoblast function 8.