Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (PubMed:18218901). Tetramer (PubMed:19345194). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is calcium independent; interaction competes with PPP3CA for NFATC2 binding; interaction is reduced by AKT activation (PubMed:18218901). Interacts with NFATC1 and NFATC4 (PubMed:18218901). Interacts with SHANK1; forms a high-order complex at least composed of SHANK1 and HOMER3; the complex formation is regulated by CAMK2A-mediated phosphorylation (PubMed:19345194). Postsynaptic density of neuronal cells. The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. Belongs to the Homer family.