FGD1, encoding a guanine nucleotide exchange factor specific for the Rho GTPase cell division cycle 42 (CDC42), is involved in multiple biological processes such as cytoskeleton restructuring, cell morphology, cell cycle progression, and membrane trafficking. It plays a crucial role in skeletal formation, embryonic morphogenesis, and extracellular matrix remodelling [5,6,7].

Mutations in FGD1 cause Aarskog-Scott syndrome (AAS), a rare X-linked genetic disorder with manifestations like short stature, facial anomalies, skeletal deformities, and genitourinary malformations [1,2,8]. In AAS patients, various FGD1 variants have been identified, and genotype-phenotype correlation analysis has provided insights into the role of FGD1 domains [1]. In vitro studies on FGD1 variants associated with AAS have shown changes in protein-protein interactions, osteogenic-related gene transcription levels, and signaling pathway activation [2]. Additionally, FGD1 has oncogenic properties in osteosarcoma and hepatocellular carcinoma. In osteosarcoma, it promotes tumor progression and regulates the tumor immune response by inhibiting PTEN activity and activating the PI3K/AKT signaling pathway [3]. In hepatocellular carcinoma, it regulates cell morphology, autophagy, and mitochondrial function [4].

In conclusion, FGD1 is essential for normal development and function through its regulation of CDC42-related processes. Studies on FGD1-related AAS and its role in cancers, using in vitro functional assays and patient-based genetic analysis, have enhanced our understanding of its biological functions and its implications in disease development, potentially guiding future therapeutic strategies for these conditions.