EFCAB9 is a calcium-binding protein that functions as a critical pH-dependent Ca2+ sensor within the CatSper channel complex, which regulates sperm hyperactivation and motility 1. As an auxiliary component of CatSper, EFCAB9 associates directly with the CATSPERζ subunit and coordinates the organization of calcium signaling nanodomains along the sperm flagellum 1. The protein exhibits dual sensing capability, responding to both intracellular Ca2+ and pH variations encountered in the female reproductive tract, with Ca2+-dependent binding to CATSPERζ that dissociates at elevated pH 1. Structurally, EFCAB9-CATSPERζ interactions are essential for maintaining the characteristic zigzag architecture of CatSper channel rows; loss of EFCAB9 disrupts this two-row channel structure and causes fragmentation and misalignment of the repeating units 2. Functionally, EFCAB9 deficiency severely impairs sperm motility and male fertility through disruption of pH-dependent CatSper activation and loss of proper Ca2+ signaling organization 12. These findings establish EFCAB9 as a long-sought intracellular pH and Ca2+ sensor triggering the motility changes necessary for successful fertilization 1.