The R22X nonsense SDHD mutation found in hereditary paraganglioma and pheochromocytoma generates a truncated SDHD protein of 21 amino acids (instead of 159), resulting in the loss of complex II electron transfer and enzymatic activities and in the activation of the HIF1α signaling pathway [64,65]. The gene discussed is SDHD; the disease is hereditary pheochromocytoma-paraganglioma.