SLC22A4 encodes OCTN1, a Na(+)- and pH-dependent membrane transporter mediating the cellular uptake of endogenous and microbial-derived organic cations 1. Its primary physiological function involves transporting the food-derived antioxidant ergothioneine, which is absorbed from the small intestine and renal tubular cells to maintain systemic ergothioneine homeostasis 2. SLC22A4 also mediates acetylcholine transport in non-neuronal tissues, supporting the cholinergic anti-inflammatory system, and may function as a low-affinity carnitine transporter 34. Ergothioneine, a thio-histidine betaine amino acid synthesized by microbes and fungi but absent in plants and animals, is recognized as a cellular antioxidant and cytoprotectant 1. SLC22A4-mediated ergothioneine transport displays a critical physiological role in controlling inflammation and oxidative stress; knockout models show increased susceptibility to oxidative damage 2. In humans, ergothioneine blood levels decline after age 60 and correlate with cognitive and cardiovascular health outcomes 2. SLC22A4 polymorphisms are associated with rheumatoid arthritis (RA) susceptibility, particularly in East Asian populations 5. Expression of SLC22A4 is regulated by RUNX1, a hematological transcription factor implicated in autoimmune disease pathogenesis 6. Additionally, SLC22A4 contributes to cationic compound transport across the blood-testis barrier and regulates drug disposition 7.