Neuron development requires an elaborate network of endosomal transport pathways, defects in which underlie multiple neurological diseases. DENND10/FAM45A is an ancient protein that is important for endosomal homeostasis. However, the role of DENND10 in the nervous system remained unknown. Here, we impaired DENND10 expression in CAD neuronal cells by CRISPR editing. DENND10 deficiency resulted in shortened neurites, which was rescued by the re-expression of DENND10. Expression levels of neuronal specific cytoskeleton protein Tubb3 and tyrosine hydroxylase (Th) were also suppressed by DENND10 deletion. Here we utilized TMT-based quantitative mass spectrometry to study the proteomic landscape of DENND10-impaired CAD neurons.