Septin12, a member of the septin family of conserved cytoskeletal GTPases, is specifically expressed in the testis. Septins have GTPase activity and are involved in various biological processes such as morphogenesis, compartmentalization, apoptosis, and cytokinesis [2]. SEPTIN12 is crucial for spermatogenesis and sperm function, with its expression regulated by androgen and estrogen receptors [3].

In mouse models, Septin12 -/- male mice are infertile, presenting reduced sperm counts and abnormal sperm morphology, while Septin12 +/- male mice are fertile, indicating that homozygous loss, not haploinsufficiency, leads to male infertility and fertilization failure [1]. Septin12 knockout mice also show that loss of PLCζ around the acrosome might be the reason for fertilization failure of Septin12 -/- sperm, and artificial oocyte activation can overcome this [1]. Chimeric mice with a defective Septin12 allele display abnormal sperm morphology, decreased sperm count, and immotile sperms [4]. Additionally, Septin12 expression levels are critical for mammalian spermiogenesis, as evidenced by the infertility of chimeras derived from 129 embryonic stem cells containing a septin12 mutant allele [5].

In conclusion, Septin12 plays an essential role in spermatogenesis and sperm function. Studies using gene knockout mouse models have revealed its significance in male fertility, specifically highlighting the impact of homozygous loss on sperm quality and fertilization ability. Understanding the function of Septin12 provides insights into the mechanisms underlying male infertility.