KCNU1 (also known as SLO3) encodes a testis-specific potassium channel that is essential for male fertility and sperm function 1. The channel is activated by both intracellular pH increases and membrane voltage, mediating potassium efflux that underlies the primary spermatozoan K+ current 2. During sperm capacitation, KCNU1 channels mediate membrane hyperpolarization triggered by the alkaline environment encountered in the female reproductive tract, which is critical for preparing sperm for fertilization 3. The channel plays an indispensable role in the acrosome reaction, a key exocytotic process required for sperm-egg penetration and fusion 4. Functional studies demonstrate that human KCNU1 channels are modulated by LRRC52, a testis-specific accessory subunit, and their activity is sensitive to pH changes 2. Clinically, bi-allelic variants in KCNU1 cause male infertility characterized by impaired acrosome reactions, despite normal sperm quantity and morphology 5. These genetic defects can be overcome through intracytoplasmic sperm injection, providing a therapeutic option for affected individuals 5. The identification of KCNU1 mutations expands our understanding of genetic causes of male infertility and provides new diagnostic markers.