Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU (PubMed:24231807). Plays a central role in regulating the uniplex complex response to intracellular calcium signaling (PubMed:27099988). Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (PubMed:27099988). Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807). Interacts (via the transmembrane region) with MCU (via the first transmembrane region); the interaction is direct (PubMed:27099988). Interacts (via the poly-Asp region) with MICU1 (via polybasic region); the interaction is direct (PubMed:27099988). Interacts (via its C-terminal poly-Asp tail) with MCUR1; the interaction is direct (PubMed:27184846). Unprocessed form interacts (via transit peptide) with MAIP1 (PubMed:27642048). MAIP1 is required to assist sorting of EMRE/SMDT1 into mitochondrion by protecting EMRE/SMDT1 against protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation by the mitochondrial processing peptidase (PMPCA and PMPCB) (PubMed:27642048). The GXXXX[G/A/S] motif at the C-terminal part of the transmembrane region mediates interaction with MCU and is required to activate the calcium-conducting pore in the uniporter complex. The poly-Asp region at the C-terminus mediates interaction with the polybasic region of MICU1. Undergoes proteolytic degradation in neurons: degraded by AFG3L2 before SMDT1/EMRE assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048). Belongs to the SMDT1/EMRE family. A publication reports an opposite topology (PubMed:26774479). However, 3 different articles, 2 in human and one in mouse, confirm the topology shown in this entry (PubMed:27099988, PubMed:27642048).