Fam20b, a protein-coding gene, is a newly identified xylose kinase. It phosphorylates xylose in the glycosaminoglycan-protein linkage region, which is essential for glycosaminoglycan (GAG) chain elongation and assembly [3]. GAGs are crucial components of the extracellular matrix (ECM), and thus, Fam20b is implicated in ECM-related biological processes.

In gene-knockout studies, inactivating Fam20b in the dental epithelium of mice led to supernumerary tooth formation. This occurs as Fam20B-catalyzed GAGs regulate Sox2⁺ dental epithelial stem/progenitor cell homeostasis by restricting FGFR2b signaling at the initial tooth development stage [1,6]. In Wnt1-Cre; Fam20bf/f mice, where Fam20b was inactivated in neural crest-derived mesenchyme, complete cleft palate, malformed tongue, and micrognathia were observed due to reduced GAG chains promoting palatal cell apoptosis and impaired osteogenesis [2,5]. Also, in Fam20B conditional knockout mice with inactivation in type I collagen-expressing cells, severe spine deformity and intervertebral disc defects were seen, along with cell fate changes in the annulus fibrosus via alterations in TGF-β and MAPK signaling pathways [4].

In conclusion, Fam20b is essential for various developmental processes. Its function in GAG chain synthesis impacts tissue morphogenesis and homeostasis. The Fam20b KO/CKO mouse models have significantly contributed to understanding its role in craniofacial development, tooth formation, and intervertebral disc development, providing insights into related congenital defects and disorders [1-2, 5, 7, 9].