Homer protein homolog 1

Homer protein homolog 1 (HOMER1) is a postsynaptic density scaffolding protein that bridges cytoplasmic regions of metabotropic glutamate receptors (GRM1, GRM5) and inositol trisphosphate receptors (ITPR1), coupling surface receptor activation to intracellular calcium release. Through these protein–protein interactions, HOMER1 supports synaptic transmission and plasticity (UniProt: Q86YM7). The protein is predominantly expressed in neuronal tissues, where it assembles high-order complexes with SHANK family proteins essential for dendritic spine structural integrity.

HOMER1 shows down-regulation in Alzheimer's disease. According to Chaparral AD proteomics analysis, HOMER1 is significantly reduced in human post-mortem AD brain compared to age-matched controls (mean log2 fold-change: −0.9971), measured across subcellular fractions by TMT-labeled quantitative proteomics. This reduction may reflect loss of synaptic scaffolding function and impaired glutamate receptor signaling, processes central to AD-associated cognitive decline and neurodegeneration.