FGD1, also known as FYVE, RhoGEF, and PH domain-containing 1, is a gene encoding a guanine nucleotide exchange factor that specifically activates the p21 GTPase Cdc42. It is involved in multiple biological processes such as cytoskeleton restructuring, cell morphology, cell cycle progression, and cell polarity, and is also associated with post-Golgi transport [5,6,8]. Mutations in FGD1 can lead to various diseases, highlighting its importance in normal physiological function [1,2,7,9].

Mutations in FGD1 cause Aarskog-Scott syndrome (AAS), a rare X-linked genetic disorder with symptoms like short stature, facial, skeletal, and genital anomalies [1,2,9]. Functional assays in cell lines and in vitro studies show that FGD1 variants can disrupt normal biological functions. For example, a specific FGD1 variant (c.1270A>G, p.Asn424Asp) led to decreased interaction with CDC42 protein, reduced transcription levels of osteogenic-related genes, and abnormal activation of JNK1, resulting in AAS [2]. In osteosarcoma and hepatocellular carcinoma, over-expression of FGD1 promotes tumor progression, indicating its oncogenic properties [3,4].

In conclusion, FGD1 is crucial for normal biological functions, especially those related to cytoskeleton regulation, cell shape, and membrane trafficking. Its dysregulation due to mutations is strongly associated with Aarskog-Scott syndrome, and abnormal over-expression contributes to the development of certain cancers. Research on FGD1, especially through functional studies in cell lines, helps us understand the molecular mechanisms underlying these diseases and may provide potential therapeutic targets.