ACAP3 (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3) is a GTPase-activating protein that negatively regulates the small GTPase Arf6 with high specificity 1. In neurons, ACAP3 promotes neurite outgrowth through its Arf6-specific GAP activity, as ACAP3 knockdown impairs neurite development, which is rescued by wild-type but not catalytically-deficient ACAP3 1. ACAP3 functions as a tumor suppressor in multiple cancers by regulating receptor trafficking and degradation. In lung adenocarcinoma, ACAP3 suppresses EGFR signaling and cell proliferation via its GAP activity, controlling EGFR recycling and lysosomal degradation 2. Similarly, in papillary thyroid carcinoma, ACAP3 overexpression inhibits cell viability, migration, and invasion while promoting apoptosis through AKT and p53 pathway modulation 3. ACAP3 expression is regulated by epigenetic mechanisms; Myc-mediated DNA hypermethylation suppresses ACAP3 in lung cancer 2, while HDAC2 negatively regulates ACAP3 in thyroid cancer 3. Genetic variations in ACAP3 associate with increased epilepsy risk, particularly affecting neuronal morphogenesis and migration 4. ACAP3 also emerges as a novel candidate susceptibility gene for breast and ovarian cancer through trans-eQTL regulatory mechanisms 5. These findings establish ACAP3 as a multifunctional regulator of neuronal development and a tumor suppressor with diagnostic and therapeutic potential.