PCSK4 (proprotein convertase subtilisin/kexin type 4) is a serine endoproteinase that cleaves hormone and protein precursors at basic amino acid-rich sites. This enzyme is predominantly expressed in male germ cells and localized to the acrosomal plasma membrane of sperm 1. In males, PCSK4 is essential for processing acrosomal proteins, particularly ADAM2, which are critical for fertilization events including sperm capacitation, acrosome reaction, and zona pellucida binding 12. PCSK4-null sperm show premature acrosome reaction and reduced zona pellucida binding capacity, rendering them infertile despite normal spermatogenesis 1. In females, PCSK4 regulates trophoblast invasiveness and placental development, likely through IGF2 processing 3, and is involved in folliculogenesis 1. Dysregulation of PCSK4 expression has clinical implications: imbalanced IGF2/PCSK4 ratios are associated with excessive "big" IGF2 production in solitary fibrous tumors causing nonislet cell tumor hypoglycemia 3. Recent genome-wide association studies identified PCSK4 as a novel genetic risk factor for severe spermatogenic failure in male infertility 4. PCSK4 represents both a potential therapeutic target for contraception and a biomarker for diagnosing unexplained infertility 15.