DENND5A encodes a protein that functions as a guanine nucleotide exchanger factor (GEF). These GEF proteins activate RAB GTPases by promoting the replacement of GDP by GTP in association with the GTPase. The DENND5A protein specifically functions as a guanine nucleotide exchange factor for the activation of RAB39. The protein is also a component of the trans-Golgi network; it is involved in calcium ion transmembrane transport and has been found to interact with RAB6 and SNX1 to regulate Golgi traffic.
The gene is associated with Epileptic Encephalopathy, Early Infantile, 49 (EIEE49), a severe autosomal recessive disorder characterized by neonatal-onset seizures, intellectual disability, global developmental delay, microcephaly, hypotonia, spasticity and facial dysmorphia.