BSPH1 (binder of sperm protein homolog 1) is an epididymal protein that promotes sperm capacitation, a maturation step essential for fertilization 1. The protein is exclusively expressed in epididymal tissues 1 and localizes to the equatorial segment, post-acrosomal segment, and neck of ejaculated sperm 1. BSPH1 contains two fibronectin type-II domains characteristic of the BSP protein family 2 and binds to phospholipid liposomes, heparin, gelatin, and low-density lipoproteins 2. Mechanistically, BSPH1 specifically promotes HDL-induced sperm capacitation through direct interaction with HDLs, increasing tyrosine phosphorylation 3, but does not facilitate BSA-induced capacitation 3. Unlike other BSP proteins, BSPH1 does not induce the acrosome reaction 4. Functionally, BSPH1 shares biochemical characteristics with seminal vesicle BSP proteins from ungulates 1, suggesting evolutionary conservation of sperm maturation mechanisms across mammals. While BSPH1's role in male fertility is established, BSPH2 knockout mice show normal fertility, suggesting functional redundancy or divergence within the BSP family 5. These findings position BSPH1 as a key regulator of lipid-mediated sperm capacitation with potential implications for understanding human male fertility.