SDHD encodes succinate dehydrogenase complex subunit D, a membrane-anchoring protein essential for mitochondrial Complex II function 12. SDHD catalyzes electron transfer from succinate to ubiquinone in the electron transport chain, contributing to oxidative phosphorylation and cellular energy metabolism 3. The protein also participates in intracellular oxygen sensing and signaling 3. Germline SDHD mutations cause paraganglioma and pheochromocytoma syndrome 1 (PGL1), with predominantly head and neck paragangliomas occurring in ~80% of carriers, though extracranial tumors appear in ~20% of patients 4. Paternally inherited SDHD mutations show 43.2% penetrance by age 60 years 5. Disease pathogenesis involves accumulated succinate acting as an oncometabolite that suppresses DNA homology-dependent repair by inhibiting histone demethylase KDM4B, impairing recruitment of DNA repair factors at break sites 6. SHDD mutations confer distinct genotype-phenotype correlations; specific variants like p.Pro81Leu display characteristic phenotypes 5. Specialized clinical management at high-volume centers is recommended given tumor multifocality risks and potential for locally aggressive disease at variable ages 4. While head-and-neck paragangliomas predominate, SDHD mutations should also be considered in bilateral pheochromocytoma evaluation in young patients 7.