Flnb, also known as Filamin B, is an actin-binding protein. It plays crucial roles in multiple biological processes such as bone formation, vascular development and remodeling, and is involved in pathways like cell cycle regulation, focal adhesion, and immune regulation [1,2,5]. Its normal function is of great importance for proper development and physiological function, and genetic models are valuable for studying its functions.

In pancreatic cancer, Flnb overexpression promotes tumor progression, is associated with immune suppression, evasion, and stemness, and knockdown inhibits cancer cell proliferation and migration in vitro and tumor growth in vivo [1]. In mice, Flnb knockout (Flnb-/ -) leads to cleft palates and skeletal defects, and a pathogenic point mutation (G1586R) in Flnb can cause abnormal skeletal segmentation, potentially through down-regulating HOX gene transcription during embryonic development [2,6]. Rare loss-of-function variants in human FLNB cause non-syndromic orofacial clefts [2]. Homozygous variants in FLNB result in spondylocarpotarsal synostosis (SCT) syndrome, a skeletal dysplasia with variable phenotypes [3,4].

In conclusion, Flnb is essential for bone development, palate formation, and skeletal segmentation, as revealed through model-based research. Its dysregulation is associated with various diseases, especially skeletal dysplasias and pancreatic cancer, highlighting the importance of Flnb-related KO mouse models in understanding these disease mechanisms.