TSSK2 is a testis-specific serine/threonine kinase essential for male fertility, predominantly expressed in testis tissue 1. During spermatogenesis, TSSK2 phosphorylates its substrate TSKS and SPAG16 protein, playing a critical role in late spermatid development, particularly in flagellogenesis and cytoplasmic reconstruction 2. In mature sperm, TSSK2 localizes to the post-acrosomal region in mice and the equatorial region and neck in human sperm, where it regulates sperm function 3. Targeted deletion of Tssk2 in mice causes infertility due to dysregulation of spermiogenesis 4. In humans, genetic variations in TSSK2 are associated with male idiopathic infertility; specifically, SNP variants c.80A>G and c.774C>T show significantly higher frequency in azoospermia and oligozoospermia patients compared to controls 1. TSSK2 dysfunction correlates with multiple infertility phenotypes including spermatogenic failure and oocyte maturation defects 5. Given its essential role in spermatogenesis, TSSK2 has been identified as a promising target for reversible male contraception, with potent selective inhibitors already developed 6.