The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight

Neurosci Biobehav Rev. 2022 May;136:104596. doi: 10.1016/j.neubiorev.2022.104596. Epub 2022 Mar 4.


Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate different signal transduction pathways within PSD, involved in motor and cognitive functions, with putative implications in psychiatric disorders. Regulation of type I metabotropic glutamate receptor trafficking, modulation of calcium signaling, tuning of long-term potentiation, organization of dendritic spines' growth, as well as meta- and homeostatic plasticity control are only a few of the multiple endocellular and synaptic functions that have been linked to Homer1. Findings from preclinical studies, as well as genetic studies conducted in humans, suggest that both constitutive (Homer1b/c) and inducible (Homer1a) isoforms of Homer1 play a role in the neurobiology of several psychiatric disorders, including psychosis, mood disorders, neurodevelopmental disorders, and addiction. On this background, Homer1 has been proposed as a putative novel target in psychopharmacological treatments. The aim of this review is to summarize and systematize the growing body of evidence on Homer proteins, highlighting the role of Homer1 in the pathophysiology and therapy of mental diseases.

Keywords: Addiction; Antipsychotics; Glutamate; Immediate early genes (IEG); Major depression; Mood disorders; Post-traumatic stress disorder; Postsynaptic density (PSD); Psychosis; Schizophrenia; Treatment resistant schizophrenia.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Carrier Proteins / metabolism
  • Dopamine* / metabolism
  • Glutamates / therapeutic use
  • Homer Scaffolding Proteins / metabolism
  • Humans
  • Mental Disorders* / metabolism
  • Signal Transduction


  • Carrier Proteins
  • Glutamates
  • HOMER1 protein, human
  • Homer Scaffolding Proteins
  • Dopamine