WBP2NL (WBP2 N-terminal like) is a testis-specific protein localized to the sperm perinuclear theca and postacrosomal sheath 1. Primary function: WBP2NL is proposed as a sperm-borne oocyte-activating factor (SOAF) that initiates intracellular calcium oscillations in eggs during fertilization 2. Mechanism: The protein operates through a WW domain-signaling pathway to mediate meiotic resumption and male pronucleus assembly 3. However, its role remains controversial; while recombinant WBP2NL activates metaphase II oocytes comparably to its ortholog WBP2 1, clinical evidence questions its diagnostic utility—sperm WBP2NL expression levels show no significant correlation with fertilization rates or reproductive outcomes in ICSI cycles 42. Disease relevance: Beyond reproduction, WBP2NL exhibits elevated expression in breast cancer tissues (90% of samples) and associates with oncogenic properties through WW domain protein interactions, potentially promoting cell survival and proliferation 56. Clinical significance: As a fertility biomarker, WBP2NL protein levels correlate with bull fertility in livestock 7, though human clinical applicability remains uncertain 4. The debate over WBP2NL versus phospholipase C zeta (PLCζ) as the primary SOAF continues, with both proteins potentially contributing to oocyte activation 38.