ARHGAP27 is a Rho GTPase-activating protein that inactivates small GTPases including CDC42 and RAC1 by converting them to their GDP-bound states, functioning in clathrin-mediated endocytosis and cytoplasmic signaling 1. The protein contains characteristic SH3, WW, PH, and RhoGAP domains 1 and exists as two isoforms generated through alternative splicing 1. ARHGAP27 demonstrates pleiotropic effects across multiple neuropsychiatric and neurodegenerative conditions. It was identified as a susceptibility gene for autism spectrum disorder (ASD) with causal associations suggesting increased ASD risk 2. ARHGAP27 appears among pleiotropic genes shared between amyotrophic lateral sclerosis and Parkinson's disease, located at the chromosome 17 risk locus 3. Additionally, ARHGAP27 was identified as a pleiotropic gene affecting both primary open-angle glaucoma and Alzheimer's disease, with retina and brain cortex expression influencing glaucoma risk 4. ARHGAP27 variants also associate with reproductive biology: missense variants correlate with higher number of children ever born but shorter reproductive lifespan, suggesting trade-offs in reproductive aging 5. ARHGAP27 was identified as a novel susceptibility locus for systemic lupus erythematosus 6 and as a pleiotropic gene linking Sjögren's disease to cardiovascular disease risk 7. These diverse associations implicate ARHGAP27 in multiple pathogenic mechanisms underlying neurodegeneration and autoimmunity.