Recent Advances on Synaptotagmin-Like Mitochondrial-Lipid Binding Protein Domain Containing Lipid Transfer Proteins

The Synaptotagmin-like mitochondrial-lipid binding protein (SMP) domain is found in a group of ER-resident lipid transfer proteins that are recruited to membrane contact sites (MCSs) by adaptors. Deciphering the molecular basis underlying the recruitment of SMP proteins to specific MCS sheds light not only on their cellular localization but also on their biological functions at these sites. Here we summarize recent advances in SMP domain-containing lipid transfer proteins, focusing on a recent study showing the localization, regulation and cellular function of a specific SMP protein named testis expressed protein 2 (Tex2). TMEM55, a potential PIP phosphatase on late endosome/lysosomal (LE/lys) membranes, was identified as an adaptor that enables the recruitment of Tex2 to ER- LE/lys MCS. In addition, we have summarized several important questions about the regulation and physiological functions of Tex2 that remained unanswered.