Recombinant Human DENND3

Background

DENN domain containing 3 (DENND3) is a guanine nucleotide exchange factor (GEF) within the DENN domain protein family, specifically activating Rab GTPases such as Rab12. By facilitating the GDP-to-GTP exchange on Rab12, DENND3 regulates a range of critical cellular processes, including endosomal trafficking, lysosomal degradation, and autophagy. These functions are vital for maintaining intracellular protein turnover, as Rab12 is involved in protein sorting, vesicle transport, and the degradation of misfolded or unnecessary proteins through the autophagy-lysosome pathway. DENND3 also plays a role in cellular stress responses, where it modulates lysosomal activity to help cells adapt to metabolic or environmental challenges. It is broadly expressed across various tissues but is particularly active in cells with high endocytic demands, such as neurons and immune cells. Dysfunction or dysregulation of DENND3 has been associated with neurodegenerative diseases and disorders of cellular proteostasis, where defective lysosomal function can lead to the accumulation of cellular debris, contributing to neuronal and systemic damage.