SLC25A27 (UCP4) is a mitochondrial inner membrane transporter that facilitates proton transport across the inner mitochondrial membrane, functioning as an uncoupling protein to dissipate excessive proton gradients during oxidative and metabolic stress 1. In neurons, it regulates glutamate-induced proton conductance in astrocytes and shifts energy metabolism toward aerobic glycolysis and lactate transfer to neurons for ATP synthesis. The protein can transport chloride ions with lower efficiency, though its precise transport mechanism remains to be fully elucidated. SLC25A27 plays a neuroprotective role by regulating reactive oxygen species production and intracellular calcium homeostasis 2. Functionally, it attenuates oxidant stress in dopaminergic neurons during pacemaking, with knockout models showing compromised calcium-induced uncoupling and increased matrix protein oxidation 3. Disease relevance is substantial: genetic variants in SLC25A27 associate with late-onset Alzheimer's disease and sporadic frontotemporal dementia risk in APOE-ε4 carriers 4, and a UCP4 haplotype correlates with ultra-resistant schizophrenia treatment outcomes 2. Additionally, SLC25A27 appears in prognostic signatures for clear cell renal cell carcinoma prognosis and oxidative stress-related pathways 5, and shows altered expression in schizophrenia associated with energy metabolism dysfunction 6.