CATSPERZ encodes an auxiliary subunit of the CatSper (cation channel of sperm) complex, which is essential for sperm hyperactivation and male fertility. As a structural component of this nine-subunit ion channel complex, CATSPERZ is required for organizing CatSper into linear quadrilateral nanodomains along the flagellum 1. Together with EFCAB9, CATSPERZ associates with the CatSper channel pore and maintains the characteristic two-row structural organization of individual channels 2. This nanodomain architecture is critical for proper calcium influx regulation and sperm rheotaxis—the ability to navigate against fluid flow, an essential behavior for fertilization within the mammalian female reproductive tract 1. Targeted disruption of Catsperz in mice reduces CatSper current and sperm rheotactic efficiency, resulting in severe male subfertility 1. Loss of CATSPERZ function prevents normal flagellar reorientation and migration, rendering the proximal flagellum inflexible and altering its 3D envelope 1. Human mutations affecting CatSper subunits, including CATSPERZ, cause male infertility with compromised fertilizing capacity, highlighting the clinical significance of this channel component 3. CATSPERZ represents a late evolutionary adaptation for reproductive success in mammals.