ALDH5A1 encodes succinate semialdehyde dehydrogenase (SSADH), a mitochondrial enzyme that catalyzes the final step in gamma-aminobutyric acid (GABA) degradation 1. The enzyme converts succinate semialdehyde to succinate, a critical step in GABA catabolism 2. Loss-of-function mutations in ALDH5A1 cause SSADH deficiency, characterized by elevated urinary 4-hydroxybutyrate and neurological dysfunction 3. Clinical manifestations include early-onset psychomotor retardation (symptom onset 1 month to 1 year), epilepsy (present in approximately two-thirds of patients by adulthood), developmental delay, and symmetric basal ganglia abnormalities on MRI 32. SSADH deficiency represents one of the most severe inherited disorders of GABA metabolism; a large Leigh syndrome cohort study identified ALDH5A1 mutations among genetic defects associated with the poorest survival (≤50% 3-year survival) 4. ALDH5A1 expression is subject to epigenetic regulation via microRNA hsa-miR-29a-3p, which modulates protein translation and mRNA stability 5. Management involves symptomatic treatment and pharmacological intervention (vigabatrin, L-carnitine, taurine) to reduce toxic metabolite accumulation 3. Recent genetic studies have identified numerous pathogenic and novel variants in ALDH5A1, expanding understanding of disease mechanisms and enabling improved molecular diagnosis.