Tpst2, or tyrosylprotein sulfotransferase 2, is an enzyme crucial for protein tyrosine O-sulfation, a post-translational modification essential for protein-protein interactions and various cellular functions [3]. This sulfation process occurs in the Golgi apparatus, and Tpst2 has been implicated in multiple biological pathways related to immunity, cancer, and normal physiological functions [1,2,3]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mice, have been instrumental in understanding its role.

In KO mouse models, Tpst2 deficiency has diverse impacts. In phagocytes, Tpst2-mediated receptor tyrosine sulfation enhances leukocidin cytotoxicity and S. aureus infection; knockdown of Tpst2 in phagocytes protects mice from S. aureus infection [1]. In cancer, genome-wide CRISPR screening in mice showed that Tpst2 loss-of-function can enhance anti-PD1 treatment efficacy by boosting IFNγ-mediated signaling and antigen presentation [2]. In pancreatic ductal adenocarcinoma (PDAC), knocking down Tpst2 in mouse PDAC cells inhibits primary tumor growth, local invasion, and metastasis [3]. Also, Tpst2-/-male mice are infertile, with sperm defective in motility and fertilization ability, likely due to lack of sulfation of RNase 9 and Mfge8 [4].

In conclusion, Tpst2 is vital for protein-protein interactions through tyrosine sulfation. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases like S. aureus infection, cancer, and infertility. Understanding Tpst2 provides insights into disease mechanisms and potential therapeutic targets for these conditions.