TBC1D21 is a testis-enriched GTPase-activating protein (RabGAP) essential for male fertility through regulation of Rab family proteins 12. During spermiogenesis, TBC1D21 localizes to the acrosomal region, neck, and sperm midpiece, where it plays critical roles in spermatid development 3. Loss of TBC1D21 causes male infertility characterized by severe defects in sperm tail structure, including abnormal mitochondrial arrangement, irregular diameter, and disrupted axoneme organization, with diminished sperm motility as a consequence 4. TBC1D21 functions as an adherence factor between mitochondria by facilitating interactions between ARMC12 and mitochondrial outer membrane proteins VDAC2 and VDAC3, thereby organizing the mitochondrial sheath that wraps around the axoneme 5. The protein likely regulates acrosome formation and cytoskeletal reorganization by inactivating RAB3A activity 3. Clinically, TBC1D21 transcript levels are significantly reduced in sperm from teratozoospermia patients compared to normozoospermic controls 4. Additionally, variants in TBC1D21 show population-specific associations with exfoliation glaucoma susceptibility in Asian populations 6.