Beyond strengthening our understanding of cytoskeletal architecture during spermiogenesis, this work also establishes a feasible therapeutic strategy for male infertility by targeting RBP-mediated signaling pathways via engineered mEVs-SKAP2 and highlights mEVs-SKAP2 as a novel, minimally invasive and highly targeted intervention with intensely translational potential for restoring sperm motility and morphology in patients with asthenoteratozoospermia. Here, SKAP2 is linked to male infertility.