GDAP2 (ganglioside-induced differentiation-associated protein 2) is a lysosomal membrane-associated protein highly expressed in the brain 1. Its primary function involves cellular stress responses, as GDAP2 knockdown in Drosophila increased sensitivity to reactive oxygen species and nutrient deprivation 2. Mechanistically, GDAP2 overexpression enhances neuronal development, increasing dendritic spine complexity and neuronal morphological complexity in hippocampal neurons 1. However, elevated GDAP2 expression dysregulates excitatory synaptic transmission, increasing miniature excitatory postsynaptic current (mEPSC) frequency and seizure susceptibility in epileptic models 1. Clinically, biallelic GDAP2 mutations cause spinocerebellar ataxia, autosomal recessive 27, characterized by progressive cerebellar degeneration with adult-onset ataxia, spasticity, and dementia 2. Neuropathological changes include cerebellar, olivary, thalamic, substantia nigra, and pyramidal tract degeneration with tau pathology 2. Loss-of-function mutations impair cellular stress responses, leading to motor dysfunction and reduced lifespan in model organisms 2. Recent genetic studies identified rare GDAP2 variants associated with Alzheimer's disease risk in Hispanic populations 3, suggesting broader neurological relevance beyond cerebellar ataxia.