Xylt1, or xylosyltransferase 1, is a glycosyltransferase that initiates the biosynthesis of sulfated glycosaminoglycan (sGAG) chains, which is crucial for proteoglycan (PG) synthesis. This process is involved in various biological pathways and is of great biological importance. Genetic models, such as KO or CKO mouse models, can be used to study its function [3].

In early-stage lung adenocarcinoma, upregulation of XYLT1 is found in metastatic recurrent lesions, correlating with poor prognosis. In vitro and in vivo experiments show that XYLT1 promotes cell survival and metastasis by activating the NF-κB pathway. Mechanistically, it interacts with IκBα, facilitating sGAG-conjugated IκBα biosynthesis, enhancing the interaction between IκBα and IKKs, and promoting IκBα proteasomal degradation [1].

In calcific aortic valve disease (CAVD), posttranslational maturation of biglycan (BGN) by XYLT1 is required for TLR3 activation. BGN then induces valvular interstitial cells to transdifferentiate into bone-forming osteoblasts through TLR3-dependent induction of type I IFNs. Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD, suggesting the importance of this pathway [2].

In Desbuquois dysplasia type 2, mutations in XYLT1 lead to a reduction in cellular PG content, indicating its role in the ossification process [3].

In summary, Xylt1 is essential for proteoglycan synthesis and is involved in multiple biological processes and disease conditions. Studies using KO/CKO mouse models and other genetic approaches have revealed its role in early-stage lung adenocarcinoma metastasis, CAVD, and Desbuquois dysplasia type 2, providing insights into potential biomarker discovery and treatment strategies for these diseases.