Arl13b, an ADP-ribosylation factor-like GTPase, is highly enriched in cilia. It functions as a guanine nucleotide exchange factor (GEF) for ARL3 in some cases. It is involved in multiple signaling pathways such as VEGFA-VEGFR2, Sonic hedgehog, and is crucial for maintaining cilia-related functions, which are essential for various biological processes [1,2,3,5].

In genetically engineered mouse models, deletion of Arl13b in the kidney leads to renal cysts and absence of primary cilia. Mice expressing a cilia-excluded variant (ARL13BV358A) develop cystic kidneys, while those with a variant lacking ARL3 GEF activity (ARL13BR79Q) have normal kidney development, indicating its role within cilia to inhibit renal cystogenesis [2,4]. Endothelial Arl13b regulates vascular development in the retina and brain, and its interaction with VEGFR2 in endothelial cells activates VEGFA-VEGFR2 signaling, promoting angiogenesis and glioma growth [1]. In the male reproductive tract, deleting Arl13b in efferent ductule epithelial cells compromises cilia architecture and functions, leading to physiological imbalances [6].

In conclusion, Arl13b plays essential roles in multiple biological processes including kidney development, angiogenesis, and male reproductive tract physiology. The study of Arl13b using gene-knockout (KO) or conditional-knockout (CKO) mouse models has significantly enhanced our understanding of its functions in these areas, providing insights into potential therapeutic targets for related diseases such as glioma and male infertility [1,2,6].