NCDN (neurochondrin) is a cytoplasmic neural protein critical for brain development and synaptic function. Molecularly, NCDN enhances cell surface localization of GRM5/mGluR5 and positively regulates its signaling 1, while acting as a negative regulator of CaMK2 phosphorylation. NCDN is required for spatial learning and neurite outgrowth, with roles in neuronal differentiation through the PI3K-Akt signaling pathway downstream of NGF 2. Additionally, NCDN interacts with SMN protein in mobile vesicles, suggesting involvement in mRNA transport and vesicle trafficking 3. Bi-allelic and de novo NCDN variants cause neurodevelopmental delay, intellectual disability, and epilepsy, with affected individuals showing impaired mGluR5-induced ERK phosphorylation and altered neuronal electrophysiology 1. NCDN haploinsufficiency contributes to frontotemporal lobar degeneration (FTLD) pathophysiology through altered FUS cytoplasmic granule dynamics 4. NCDN antibodies are associated with autoimmune cerebellar ataxia, responsive to immunotherapy 5. Conditional Ncdn knockout in mice produces epileptic seizures, depressive-like behaviors, and learning impairment, confirming NCDN's essential role in normal brain function.