SULT4A1 is a brain-specific cytosolic sulfotransferase with atypical enzymatic properties and emerging roles in neuroprotection and synaptic function. While structurally similar to other sulfotransferases, SULT4A1 exhibits very low catalytic activity toward classical SULT substrates 1. The enzyme is highly expressed in selective brain regions including cerebral cortex, cerebellum, pituitary, and brainstem 2, and localizes to both cytosol and outer mitochondrial membranes 3. Mechanism-wise, SULT4A1 stability is regulated by ERK1-mediated phosphorylation at Thr11, enabling Pin1 binding and subsequent protein phosphatase 2A-catalyzed dephosphorylation 4. Notably, homodimerization protects SULT4A1 from polyubiquitination-mediated degradation 5. At the synaptic level, SULT4A1 negatively regulates Pin1 activity toward PSD-95, facilitating NMDAR synaptic expression and dendritic spine formation 6. Recent functional studies demonstrate SULT4A1-dependent, sulfate-dependent antioxidant activity that protects mitochondria from oxidative stress 3. Clinically, SULT4A1 gene variants correlate with schizophrenia and Phelan-McDermid syndrome 7. SULT4A1 knockout mice exhibit hampered neuronal development and behavioral deficits 7, suggesting its importance in neurodevelopmental disorders. Despite structural SULT classification, no physiological enzymatic substrate has been identified 7.