CAPZA3 encodes an F-actin capping protein that binds to the barbed (fast-growing) ends of actin filaments in a calcium-independent manner, blocking subunit exchange without severing filaments [UniProt]. The protein localizes to the actin cytoskeleton and plays critical roles in spermatogenesis and cellular DNA repair. In male fertility, CAPZA3 is essential for spermatid morphogenesis and spermiogenesis. It shares a bidirectional promoter with PLCζ (phospholipase C zeta), and coordinated expression of both genes correlates with fertilization success 1. CAPZA3 expression is significantly downregulated in cryptorchid testes, where it emerges as a hub gene linked to progressive loss of spermatogenesis with disease duration 2. The protein's role in actin polymerization during spermatogenesis is supported by observations that CAPZA3 transcript levels increase during postmeiotic germ cell development 3. Beyond reproduction, CAPZA3 functions in homology-directed DNA repair (HDR) within cancer cells. CAPZA3 inactivation impairs HDR capacity, increasing sensitivity to radiation and chemotherapy while paradoxically promoting resistance to CD8 T cell killing through STING pathway activation 4. CAPZA3 expression correlates with immune pathway activation and CD8 T cell infiltration in tumors 4. These findings identify CAPZA3 as a modulator of therapeutic responses in cancer immunotherapy and radiation treatment 5.