Xylt1, short for xylosyltransferase 1, is a glycosyltransferase that initiates the biosynthesis of sulfated glycosaminoglycan (sGAG) chains. It is involved in proteoglycan (PG) biosynthesis, a process crucial for various biological functions such as cell-matrix interactions, cell signaling, and tissue development [3].

In early-stage lung adenocarcinoma, upregulation of Xylt1 in metastatic recurrent lesions correlated with poor prognosis. In vitro and in vivo experiments showed that Xylt1 promoted cell survival and metastasis by activating the NF-κB pathway. Mechanistically, it interacted with IκBα, facilitated sGAG-conjugated IκBα biosynthesis, enhancing its interaction with IKKs and leading to proteasomal degradation of IκBα [1].

In aortic stenosis, post-translational maturation of biglycan (Bgn) by Xylt1 is required for TLR3 activation, and Bgn induces transdifferentiation of valvular interstitial cells into osteoblasts through TLR3-dependent induction of type I IFNs. Genetic variation at loci relevant to the Xylt1-Bgn-TLR3-IFNAR1 pathway is associated with calcific aortic valve disease (CAVD) [2].

Mutations in Xylt1 are responsible for Desbuquois dysplasia type 2, leading to a significant reduction of cellular PG content [3].

In hepatic fibrosis, a long non-coding RNA LINC01711 promoted cell proliferation and migration by increasing Xylt1 expression, which is important for constructing the extracellular matrix (ECM) [4].

In summary, Xylt1 plays essential roles in multiple biological processes and diseases. Its functions in promoting metastasis in early-stage lung adenocarcinoma, mediating aortic stenosis, and being associated with Desbuquois dysplasia type 2 and hepatic fibrosis are revealed through various in vitro and in vivo studies. These findings help understand the biological functions of Xylt1 and provide potential targets for related disease treatment [1,2,3,4].