{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CATSPER2 encodes a sperm‐specific ion channel subunit that is essential for mediating the calcium influx required for the hyperactivation of sperm motility—a specialized movement pattern critical for sperm penetration of the egg’s protective investments and, ultimately, male fertility. Studies in both murine models and human patients have shown that disruption or deletion of CATSPER2 abolishes the depolarization‐evoked Ca²⁺ entry in the sperm flagellum, leading to a failure to initiate hyperactivated motility even though basic initiation of movement and spermatogenesis are unaffected."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CATSPER2 appears to be part of an interdependent heteromeric channel complex, as its loss not only abolishes Ca²⁺ currents but also destabilizes the expression of other CatSper subunits such as CATSPER1. This co‐dependent assembly is crucial for proper channel function and the precise Ca²⁺ signaling required during sperm capacitation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, CATSPER2 has been reported to interact with other calcium channels (for example, modulating T‐type currents via associations with Ca(v)3.3), thereby further contributing to the regulation of sperm flagellar activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, mutations or copy‐number variations affecting CATSPER2 have been identified in patients with idiopathic infertility and asthenozoospermia, where reduced CATSPER2 expression correlates with impaired sperm motility. Notably, contiguous gene deletions that remove CATSPER2 along with neighboring genes (such as STRC) have been linked to syndromic presentations combining sensorineural hearing loss with male infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " Furthermore, developmental studies reveal that CATSPER2 transcripts are enriched in highly motile sperm fractions, underscoring its role in the acquisition of hyperactivated motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CATSPER2 is a crucial component of the sperm’s Ca²⁺ signaling machinery—its proper expression and function are indispensable for hyperactivation and male fertility, making it a promising target for both diagnostic assessments of idiopathic male infertility and the development of male contraceptives.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huayu Qi, Magdalene M Moran, Betsy Navarro, et al. 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