ARHGAP32 is a Rho GTPase-activating protein that negatively regulates small GTPases including RhoA, Cdc42, and Rac1 1. The protein localizes to multiple cellular compartments including the cytosol, Golgi apparatus, and postsynaptic density, where it regulates actin dynamics and dendritic spine morphogenesis 2. A key functional feature is its G-actin-binding RPEL motif, which provides negative feedback coupling Rac/Cdc42 activity to actin availability 2. ARHGAP32 is enriched in desmosomal structures through interaction with desmoplakin, where it regulates F-actin organization and epithelial cell sheet integrity by suppressing ROCK-dependent actomyosin contractility 1. Pathologically, de novo loss-of-function mutations in ARHGAP32 are associated with autism spectrum disorder 3, while a gain-of-function L754V mutation causes focal segmental glomerulosclerosis by inducing podocyte damage through altered Cdc42 binding affinity 4. ARHGAP32 dysregulation also contributes to neurodegenerative diseases, with aberrant cryptic splicing of ARHGAP32 identified as a biomarker in TDP-43 proteinopathies 5. Additionally, dysregulation of circular ARHGAP32 promotes atherosclerosis through miR-665-dependent signaling 6.