DENND2A encodes a guanine nucleotide exchange factor (GEF) that activates RAB9A and RAB9B by promoting GDP-to-GTP exchange, facilitating conversion of inactive Rab proteins to their active forms. It functions in retrograde transport from late endosomes to the trans-Golgi network and interacts with the actin cytoskeleton in the cytosol. Based on limited published evidence, DENND2A plays roles in hepatitis B virus maintenance in host cells 1 and variants in DENND2A are associated with intellectual disability and developmental delay 2, though the mechanistic basis of these disease associations requires further investigation.