Homer scaffold protein 2 (HOMER2)

Homer scaffold protein 2 (HOMER2) is a postsynaptic density scaffolding/adaptor protein widely expressed in the central nervous system and other tissues, including the inner ear, skeletal muscle, heart, and others. It regulates synaptic signaling by physically linking and cross-linking various partner proteins—principally group 1 metabotropic glutamate receptors (mGluR1/GRM1, mGluR5/GRM5), inositol trisphosphate receptors (ITPR1), ryanodine receptors (RYR1/2), SHANK proteins, and elements involved in calcium signaling and cytoskeleton organization. HOMER2 enables dynamic regulation of synaptic plasticity, calcium signaling, and actin cytoskeletal structure, especially in glutamatergic synapses and sensory hair cells. Pathogenic variants in HOMER2 are causatively linked to autosomal dominant non-syndromic sensorineural hearing loss (DFNA68), and functional disruption leads to progressive hearing impairment. The protein contains an EVH1 domain for recognizing proline-rich target sequences and a coiled-coil domain facilitating multimerization and protein–protein interactions. HOMER2 is not a classical receptor, enzyme, transporter, or druggable target by conventional pharmacological standards, and there are no reported drugs that act directly on it.

Other names

Homer protein homolog 2Homer-2CupidinVesl-2HOMER-2BHOMER-2ADFNA68ACPDCPDVESL-2homer protein homolog 2cupidinhomer homolog 2homer homolog 3homer scaffolding protein 2neuronal immediate early gene 2