SDHA (succinate dehydrogenase complex flavoprotein subunit A) is the flavoprotein subunit of complex II of the mitochondrial electron transport chain, responsible for transferring electrons from succinate to ubiquinone 12. This catalytic activity is essential for both aerobic respiration and the tricarboxylic acid cycle. Beyond its metabolic role, SDHA functions as a tumor suppressor 3. Germline SDHA mutations predispose to multiple neoplasms. SDHA pathogenic variants account for up to 10% of pheochromocytoma/paraganglioma cases and 30% of wild-type gastrointestinal stromal tumors (GISTs) 45. SDHA-associated tumors typically present across wide age ranges (11-81 years) with single tumors predominating (91%), particularly in head/neck (46%) or abdominal locations (43%), and metastatic disease occurring in 25.5% of cases, predominantly to bone and lymph nodes 6. Penetrance is relatively low (~39% by age 40) and significantly lower in asymptomatic relatives (13%) compared to index patients (45%) 7. SDHA deficiency disrupts genome integrity through oncometabolite accumulation. Elevated succinate suppresses homology-directed DNA repair by inhibiting the lysine demethylase KDM4B, causing aberrant histone methylation that impairs recruitment of critical repair factors like TIP60 and ATM 8. Additionally, SDHA dysfunction contributes to disease through metabolic reprogramming—succinate accumulation stabilizes HIF-1α in lung fibrosis 9 and disrupts the SIRT3-SDHA-OXPHOS axis critical for immune cell differentiation 10.