Cation channel sperm-associated protein 4 (CATSPER4)

Cation channel sperm-associated protein 4 (CATSPER4) is a pore-forming subunit of the CatSper complex, a unique, sperm-specific, tetrameric voltage-gated calcium (Ca2+) channel essential for hyperactivated sperm motility and male fertility[1][3][4]. CATSPER4, along with CATSPER1–3 and several auxiliary proteins, assembles into a structured nanodomain along the sperm flagellum, enabling regulated Ca2+ entry in response to physiological cues, such as changes in pH and signals from the female reproductive tract[1][3][4]. Genetic loss or disruption of CATSPER4 abolishes CatSper channel function and leads to asthenozoospermia (immotile sperm) and male infertility in mice and humans[1][4]. CATSPER4 does not act as an independent functional channel but is strictly required as a component of the multimeric CatSper complex; its correct assembly, trafficking, and domain organization are crucial for sperm to gain the hyperactivation movement required to reach and fertilize the oocyte[1][3]. CatSper channel activity can be modulated by molecules such as pregnenolone sulfate (agonist) and blocked by compounds such as pristimerin or lupeol (inhibitors), which has raised interest in CatSper subunits as potential targets for male contraception and as biomarkers for sperm function[4].

Other names

CatSper4CATSPER4cation channel sperm-associated 4ion channel CatSper4

Modulation of CatSper channel activity to increase or decrease Ca2+ influx in sperm, affecting sperm motility and fertilization capacity