TSSK

TSSK, or testis-specific serine/threonine kinase, belongs to the calcium/calmodulin kinase (CAMK) superfamily. It is a family of protein kinases specifically expressed in the testes and primarily regulate spermatogenesis and fertilization. This family contains six subtypes (TSSK1-TSSK6). In humans, TSSK5 is a pseudogene, and there is also a primate-specific pseudogene, TSSK1B. The core functional subtypes are TSSK1, TSSK2, TSSK3, TSSK4, and TSSK6. TSSK1/2 have the highest homology and similar structure, while TSSK3/4/6 contain only kinase domains. Key interactions/upstream and downstream targets include the substrate TSKS, the molecular chaperone HSP90, the upstream kinase PDK1, and the downstream substrates Odf2, CREB, and histones. TSSK1/2 specifically phosphorylates TSKS, TSSK4 phosphorylates Odf2 and CREB, TSSK6 participates in histone phosphorylation, and HSP90 is responsible for stabilization and activation. TSSK family kinases, PDK1 activates TSSK3; TSSK family is specifically expressed in the testes and mainly functions in sperm cells after meiosis. TSSK1/2/6 regulate sperm morphology, chromatin remodeling, and sperm-egg fusion. TSSK4 maintains sperm flagella structure and motility. TSSK3 is specifically expressed in testicular Ledich cells. Related disease areas focus on male infertility (oligospermia/asthenospermia/azoospermia, sperm abnormalities, fertilization disorders). At the same time, abnormal expression of TSSK2/3/6 is related to tumor proliferation and survival, and is a potential target for cancer research^[1][2][3].