Fam20b, a member of the FAM20 kinase family, is a xylose kinase essential for glycosaminoglycan (GAG) assembly [3]. It phosphorylates the xylose residue in the glycosaminoglycan-protein linkage region, regulating the number of GAG chains [3]. GAGs are crucial components of the extracellular matrix (ECM), involved in various biological processes like signal molecule enrichment and ligand-receptor binding regulation [5].

In mouse models, inactivation of Fam20b in different tissues reveals its diverse roles. In dental epithelium, disruption of Fam20b-catalyzed GAGs leads to supernumerary tooth formation by affecting Sox2⁺ dental epithelial stem/progenitor cell homeostasis and restricting FGFR2b signaling [1,6]. In neural crest-derived mesenchyme, its inactivation causes multiple craniofacial defects including cleft palate, micrognathia, and reduced mineralization [2,5]. In type I collagen-expressing cells of the intervertebral disc annulus fibrosus, Fam20b inactivation results in disc defects and cell fate changes via alterations in TGF-β and MAPK signaling pathways [4].

In conclusion, Fam20b is vital for the proper development and function of multiple tissues through its role in GAG synthesis. The study of Fam20b knockout or conditional knockout mouse models has significantly contributed to understanding its functions in craniofacial development, tooth formation, and intervertebral disc development, providing insights into related disease mechanisms [1,2,4,5,6].