Slc25a27, also known as uncoupling protein 4 (UCP4), is a member of the mitochondrial uncoupling protein family. It is involved in regulating mitochondrial superoxide and ATP production, acting as a proton transporter. Neuronal uncoupling proteins, including Slc25a27, play a role in regulating reactive oxygen species production and intracellular calcium homeostasis, potentially having a neuroprotective function [1,2].

In mouse models, systemic kanamycin challenge led to a significant up-regulation of Slc25a27 mRNA in spiral and vestibular ganglia, an effect blocked by co-administration of the antioxidant 2,3-dihydroxybenzoate. This suggests that Slc25a27 upregulation in the inner ear ganglia may be a secondary response to kanamycin-induced hair cell death, and increased Slc25a27 expression may have neuroprotective effects via reduction in mitochondrial superoxide generation [2]. In addition, a haplotype spanning UCP4 (Slc25a27) was found to be significantly under-represented in patients with ultra-resistant schizophrenia, indicating its possible influence on treatment outcome in schizophrenia [1]. In autism, SLC25A27 showed consistently reduced expression in the anterior cingulate gyrus, motor cortex, and thalamus of patients and genetic association with autism in Japanese samples [3].

In summary, Slc25a27 is important for mitochondrial function and may play a role in neuroprotection. Studies in mouse models and human disease samples have revealed its potential involvement in conditions such as inner ear damage-related responses, schizophrenia treatment outcomes, and autism, highlighting its significance in understanding these biological processes and diseases.