ALDH3A2 (fatty aldehyde dehydrogenase) catalyzes the oxidation of medium and long-chain aliphatic aldehydes (6-24 carbons) to their corresponding fatty acids 1. It functions as a membrane-bound protein involved in fatty acid oxidation and is responsible for converting sphingosine 1-phosphate degradation products, including hexadecenal to hexadecenoic acid 2. The enzyme operates primarily through NAD+-dependent oxidation mechanisms and exhibits long-chain fatty aldehyde dehydrogenase activity 3. Mutations in ALDH3A2 cause Sjögren-Larsson syndrome (SLS), an autosomal recessive disorder characterized by ichthyosis, mental retardation, and spastic diplegia 4. Disease pathogenesis involves structural disturbance and impaired metabolite clearance, leading to abnormal lipid accumulation that disrupts multilamellar membrane formation in skin and myelin 35. Missense mutations (38% of identified mutations) predominantly reduce enzyme activity, while deletions and splice-site mutations account for additional disease mechanisms 4. Beyond SLS, ALDH3A2 expression alterations associate with pulmonary arterial hypertension and gastric adenocarcinoma prognosis 67. In colorectal cancer, ALDH3A2 upregulation via PI3K/AKT signaling promotes lipid accumulation and metastasis 8. These findings suggest ALDH3A2's broader roles in cellular metabolism regulation and disease pathogenesis.