Protein palmitoylation in spermatogenesis and sperm function: emerging roles and regulatory mechanisms

Spermatogenesis, a complex developmental process, is spatiotemporally regulated by post-translational modifications. Among these, dynamic protein palmitoylation emerges as a central coordinator of membrane-associated events, critically governing acrosome formation, tail assembly, blood-testis barrier integrity, and epididymal maturation. This review synthesizes current knowledge on how palmitoylation, catalyzed by ZDHHC enzymes and reversed by thioesterases, regulates protein localization, stability, and interactions to ensure normal sperm production and function. Disruption of this modification is linked to sperm defects and male infertility. We further highlight the unique expansion of the testicular palmitoylome and explore its potential as a target for novel diagnostic biomarkers and reversible male contraceptives. Unresolved questions regarding enzyme-specific functions, crosstalk with other modifications, and roles in meiosis are discussed to guide future research.