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. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoform 1 regulates the trafficking and surface expression of GRM5. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 5 counteracts the effects by competing for binding sites. Isoform 3 regulates the trafficking and surface expression of GRM5. Isoform 5 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, isoform 2 and isoform 3 to regulate synaptic metabotropic glutamate function. Isoform 5, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development (By similarity). Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). 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 (By similarity). Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). Isoform 1, isoform 2 and isoform 3 encode a coiled-coil structure that mediates homo- and heteromultimerization (By similarity). Interacts with GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2 and SHANK3 (PubMed:12379179, PubMed:21558424, PubMed:24153177). Interacts with IFT57 and OPHN1 (PubMed:17107665). Interacts with SHANK1; forms high-order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent (By similarity). Interacts with NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (By similarity). Interacts with SRGAP2 (PubMed:27373832). Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum. The N-terminal of isoform 2 may facilitate trafficking of the complex with GRM5 from the endoplasmic reticulum (ER) to the plasma membrane (PM). Isoform 1, isoform 3 and isoform 5 are expressed in skeletal muscle at the level of the Z line, in heart, forebrain and cerebellum. Isoform 2, is a minor isoform and is expressed in cardiac and skeletal muscle. Isoform 5 is expressed in the postsynaptic region of neurons. The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (By similarity). Belongs to the Homer family.