SEMG1 (semenogelin 1) is a multifunctional secretory protein primarily expressed in male germ cells with critical roles in reproductive function and disease pathology. In the reproductive tract, SEMG1 is a major component of seminal plasma that forms a gel matrix encasing ejaculated spermatozoa 1. It regulates sperm motility through interaction with the sperm-associated protein EPPIN, leading to transient inhibition of sperm motility after ejaculation 2. Proteolytic degradation of SEMG1 by prostate-specific antigen (PSA) facilitates semen liquefaction, essential for normal sperm function 3. Additionally, SEMG1 promotes sperm survival in the female reproductive tract 1. Elevated SEMG1 expression is strongly associated with asthenozoospermia (reduced sperm motility) and male infertility; miR-525-3p directly suppresses SEMG1 expression, and low miR-525-3p levels correlate with high SEMG1 and infertility 4. As a cancer-testis antigen, SEMG1 is aberrantly overexpressed in various malignancies including lung, prostate, renal cancers, and oral squamous cell carcinoma, where it promotes tumorigenesis 56. Mechanistically, SEMG1 augments cancer cell energy metabolism by enhancing pyruvate kinase M2 and lactate dehydrogenase A activity, increasing glycolysis, mitochondrial membrane potential, and reactive oxygen species production 56. Emerging evidence suggests SEMG1 as a potential therapeutic target for male infertility treatment and male contraception 43.