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Spermatogenesis-associated protein 33 (SPATA33) is a testis-enriched protein specifically expressed in spermatogenic cells—including spermatogonia, spermatocytes, round spermatids, and spermatozoa—where it plays key roles in mitophagy and sperm motility[1][2][3][5]. SPATA33 mediates the removal of damaged mitochondria, maintaining mitochondrial homeostasis during spermatogenesis, and is required for normal sperm midpiece flexibility, essential for motility and male fertility[1][3][5]. Mechanistically, SPATA33 interacts with sperm calcineurin (a calcium-dependent phosphatase critical for male fertility) through a conserved motif, localizes this complex to the mitochondria via interaction with the outer mitochondrial membrane protein VDAC2, and is indispensable for the correct positioning and function of calcineurin in sperm[3][5]. Disruption of SPATA33 results in reduced sperm motility due to inflexible sperm midpieces, phenocopying defects seen in sperm calcineurin knockout models and causing male infertility[3][5]. No drugs are currently known to target SPATA33 directly, and it is not a therapeutic target, receptor, enzyme, or transporter.
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