S-palmitoylation, a lipid posttranslational modification, is involved in diverse cellular processes across biological systems. However, whether S-palmitoylation is pivotal for male reproduction was unknown.

This work, led by Yuki Kaneda, Haruhiko Miyata, Masahito Ikawa (RIMD, Osaka University), and Yonggang Lu (WPI-PRIMe, Osaka University), for the first time, demonstrates the essential role of S-palmitoylation in sperm morphogenesis. The team identified a regulatory pathway, in which TEX38 stabilizes and localizes ZDHHC19, a testis-specific palmitoyltransferase, to the plasma membrane of male germ cells, thereby ensuring the downstream palmitoylation of ARRDC5. Disruption of this TEX38–ZDHHC19–ARRDC5 axis results in sperm malformation and male sterility.

This discovery of a germline-specific, ZDHHC19-mediated posttranslational modification pathway sheds light on the diagnosis of idiopathic male infertility and the development of nonhormonal male contraceptives.

Title	TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice
Authors	Yuki Kaneda#, Yonggang Lu#,*, Jiang Sun#, Keisuke Shimada, Chihiro Emori, Taichi Noda, Takayuki Koyano, Makoto Matsuyama, Haruhiko Miyata*, Masahito Ikawa* # Co-first authors; * Co-corresponding authors
DOI	https://doi.org/10.1073/pnas.2417943122
Journal	Proceedings of the National Academy of Sciences
Published date	March 3, 2025