Slc22a4, also known as OCTN1, is an organic cation transporter. It plays a crucial role in the absorption and distribution of ergothioneine (ERGO), a food-derived antioxidant. ERGO is hydrophilic, and its entry into various organs, including the brain, is mediated by Slc22a4. This transporter is also involved in the renal reabsorption of ergothioneine [1,2,3].

In Octn1 gene knockout mice, ERGO is absent in the brain due to the lack of OCTN1 in neurons, neural stem cells, and microglia. This indicates that Slc22a4-mediated ERGO uptake is vital for brain function. Oral administration of ERGO shows antidepressant activities in mice, and repeated oral intake of ERGO or ERGO-containing food extract tablets enhances memory function in mice and humans, respectively. Also, ERGO protects against stress-induced sleep disturbance and neuronal injury induced by amyloid β in rodents [1].

In conclusion, Slc22a4 is essential for the distribution of ergothioneine, especially in the brain. The study of Octn1 gene knockout mice has revealed its role in maintaining brain function, such as in promoting memory and protecting against neuronal injury. This suggests its potential significance in treating neurological disorders related to oxidative stress and neurodegeneration [1].