The structural basis of CatSper function in sperm motility and fertilization.

Cation channel of sperm (CatSper) is the principal Ca2+ entry pathway governing sperm hyperactivated motility, a process essential for successful fertilization and male fertility in sexually reproducing animals. Recent structural studies of native mouse CatSper, together with in situ analyses in mouse and human sperm, have transformed our understanding of how its unique multisubunit architecture underpins channel assembly, gating, and higher-order organization along the sperm flagellum. These advances have also provided insights into the evolutionary diversification of CatSper and the spatial organization of Ca2+ signaling required for sperm function. In this review, we summarize recent progress in elucidating CatSper structure, mechanism, evolution, and physiological function, and discuss the implications for male infertility and the structure-guided development of nonhormonal male contraceptives.