RABL2B is a small GTPase essential for ciliary assembly and function. It operates through an intrinsic GDP-to-GTP nucleotide exchange mechanism independent of traditional GTPase exchange factors 1. The primary mechanism involves RABL2B binding to the intraflagellar transport (IFT) complex B at the ciliary base, triggering entry of pre-docked IFT-B complexes into the cilium 12. RABL2B also positively regulates localization of ciliary G-protein-coupled receptors (GPCRs) such as GPR161 and HTR6 by physically associating with these receptors at the ciliary base 3. The protein is recruited to the mother centriole through interactions with distal appendage proteins CEP164 and CEP83, and functions with CEP19 to coordinate IFT entry 13. Clinically, RABL2B variants associate with male infertility; the intronic rs144944885 delC variant shows elevated frequency in oligoasthenoteratozoospermia patients and predicted to alter pre-mRNA splicing 4. In Phelan-McDermid syndrome, RABL2B deletion as part of Class I deletions correlates with cognitive and psychiatric phenotypes distinct from Class II deletions 5. RABL2B demonstrates preferential expression in human brain and placenta compared to its paralog RABL2A, suggesting non-redundant functional importance 6. Reduced RABL2B expression associates with poorer pancreatic cancer survival 7, and it appears as a candidate biomarker in thyroid cancer 8 and Alzheimer's disease pathogenesis 9.