PLCZ1 (phospholipase C zeta 1) is a sperm-specific phospholipase C enzyme that serves as the predominant oocyte-activating factor in mammalian fertilization 1 2. The protein functions by hydrolyzing phosphatidylinositol-4,5-bisphosphate (PIP2) to generate inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), triggering intracellular calcium oscillations essential for oocyte activation 3. PLCZ1 comprises four N-terminal EF-hand domains responsible for calcium sensitivity, X and Y catalytic domains that cleave PIP2, an XY-linker region, and a C-terminal C2 domain that facilitates membrane anchoring 3. Clinically, PLCZ1 deficiency is the leading cause of fertilization failure after intracytoplasmic sperm injection (ICSI), affecting 1-3% of cycles 1 4. Multiple pathogenic variants throughout the PLCZ1 gene have been identified in infertile males, with frequencies reaching 29.09% in patients experiencing fertilization failure 5. Novel mutations including compound heterozygous variants have been linked to both partial and total fertilization failure 6. These defects can be successfully treated with assisted oocyte activation using calcium ionophores, significantly improving fertilization and live birth rates 5 4, making PLCZ1 both a diagnostic marker and therapeutic target for male infertility.