Homer1, a synaptic scaffold protein, is crucial for regulating glutamatergic synapses and spine morphogenesis [4]. It interacts with various proteins like metabotropic glutamate receptors (mGluRs), modulating calcium signaling, long-term potentiation, and dendritic spine growth. It also plays a part in integrating different signal transduction pathways within the postsynaptic density, being involved in motor and cognitive functions [2].

In disease-related studies, Homer1 has shown significant impacts. In intracerebral hemorrhage (ICH) models, overexpression of Homer1 promotes the conversion of A1 astrocytes (associated with neuroinflammation) to A2 astrocytes (neuroprotective), inhibits MAPK signaling activation, and improves outcomes, associated with changes in inflammatory and anti-inflammatory factors [1]. In middle cerebral artery occlusion-induced retinal ischemia models, Homer1 overexpression protects retinal ganglion cells from pyroptosis by inhibiting endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation [3]. In ischemic stroke models, knockdown of Homer1 promotes neuronal death by enhancing necroptotic signaling and inflammation, while injection of Homer1 protein reduces injury and improves outcomes [5]. In chronic social stress models, disruption of Homer1/mGluR5 coupling is observed, and Homer1 knockout mice show hyperactivity and hypothalamic-pituitary-adrenal axis dysregulation [6].

In conclusion, Homer1 is essential for synaptic function and spine stability. Through gene knockout (KO) and other genetic models, its role in various disease conditions such as ICH, retinal ischemia, ischemic stroke, and stress-induced psychiatric disorders has been revealed. These models have provided insights into potential therapeutic targets related to Homer1 in treating these diseases.