Abstract
Protein lipidation, a pivotal post-translational modification, dynamically regulates cellular signaling, membrane trafficking, and protein stability, with emerging roles in reproductive physiology. However, the systematic understanding of how distinct lipid modifications orchestrate physiological processes in male and female reproduction remains incomplete. This review systematically elaborates the mechanistic contributions of protein lipidation to gametogenesis, fertilization, and reproductive homeostasis. Finally, we discuss emerging therapeutic strategies targeting lipidation pathways-including inhibitors of palmitoylation (2-BP) and prenylation (lonafarnib)-and highlight their potential for treating infertility and reproductive disorders.