DTNB (dystrobrevin beta) is a scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids. It functions as a repressor of the SYN1 promoter through binding of repressor element-1 (RE-1), regulating SYN1 expression and potentially involved in cell proliferation during early neural differentiation 1. DTNB may be required for proper maturation and function of inhibitory synapses. Mechanistically, DTNB participates in synaptic signaling and postsynaptic density organization through protein-binding interactions at the plasma membrane and within the nucleus and cytoplasm. Clinically, DTNB has emerged as disease-relevant in neurodegeneration. Rare variants in DTNB associate with Alzheimer's disease (AD) with genome-wide significance in region-based whole-genome sequencing analysis 2. Furthermore, rare variants in DTNB associate with an AD cerebrospinal fluid biomarker profile characterized by neuronal injury and inflammation, as indicated by elevated neurofilament light chain (NfL) and YKL-40 3. Mediation analysis suggests DTNB variants affect dementia symptoms via inflammation and injury pathways, potentially by altering cytoskeleton structure. These findings identify DTNB as a novel AD susceptibility gene linked to neuroinflammatory processes in neurodegeneration.