MADD (MAP kinase activating death domain) is a multifunctional protein that serves as a guanyl-nucleotide exchange factor for small GTPases of the Rab family, particularly RAB27A, RAB27B, and RAB3 proteins involved in synaptic vesicle exocytosis and neurotransmitter release 1. The protein plays a dual role in both neurotransmission and neuroprotection, regulating Ca2+-dependent neurotransmitter release under normal conditions while blocking neuronal apoptosis under cytotoxic stress 1. MADD is also involved in TNFA-mediated activation of the MAPK pathway, including ERK1/2 signaling 2. Disease associations include multiple acyl-CoA dehydrogenase deficiency (MADD), a metabolic disorder affecting fatty acid oxidation that can present as late-onset myopathy with muscle weakness and elevated creatine kinase 34. Remarkably, riboflavin treatment shows dramatic therapeutic response in MADD patients 4. Genetic variants in MADD have been identified as candidates for intellectual disability 5 and the gene has been associated with fasting glucose homeostasis and type 2 diabetes risk 6. Reduced MADD expression has been observed in Alzheimer's disease brains, suggesting its importance in neuroprotection 1.