IQSEC3 (IQ motif and Sec7 domain ArfGEF 3) functions as a guanine nucleotide exchange factor (GEF) for ARF proteins, playing a critical role in inhibitory synapse formation and maintenance 1. The protein directly interacts with gephyrin, a key scaffold protein at GABAergic synapses, and this interaction is essential for IQSEC3's synaptic localization 1. IQSEC3 also associates with glycine receptor complexes through gephyrin binding, forming GlyR α1β-GPHN-IQSEC3 complexes at glycinergic synapses 2. Functionally, IQSEC3 overexpression increases inhibitory synapse density in an ARF-GEF activity-dependent manner, while its knockdown reduces GABAergic synaptic density and decreases gephyrin cluster size 13. Loss of IQSEC3 disrupts GABAergic synapse maintenance, increases seizure susceptibility, and selectively depletes somatostatin peptides in hippocampal interneurons 3. Clinically, IQSEC3 has been implicated in neurodevelopmental disorders, with deletions associated with autism spectrum disorder 4 and variants identified as candidate genes for fetal akinesia 5. The protein has also been identified as a potential prognostic biomarker in breast cancer 6 and glioma-related epilepsy 7.