 NL2, interacting cofactor for lumicrine signaling, nickel, is a small secreted protein that is essential for proper sperm maturation and male fertility. It interacts with the testasecreted protein NL2, which is then transported through the bloodstream to the epididymis. In males lacking nickel, this process does not occur, resulting in impaired epididymal differentiation and deficient sperm maturation. By expressing nickel in testicular germ cells, researchers were able to restore normal sperm maturation and male fertility. This study demonstrates the importance of lumicrine signaling in the epididymis for successful sperm maturation and male fertility. This article was authored by Daiji Kiyozumi, Kentoro Shimoda, Michael Chalak, and others.