Solute Carrier Family SLC41, what do we really know about it?

The 41^st family of solute carriers (SLC41) comprises three members A1, A2 and A3, which are distantly homologous to bacterial Mg²⁺ channel MgtE. SLC41A1 was recently characterized as being an Na⁺/Mg²⁺ exchanger (NME; a predominant cellular Mg²⁺ efflux system). Little is known about the exact function of SLC41A2 and SLC41A3, although, these proteins have also been linked to Mg²⁺ transport in human (animal) cells. The molecular biology (including membrane topology, cellular localization, transcriptomics and proteomics) of SLC41A2 and SLC41A3 compared with SLC41A1 has only been poorly explored. Significantly more data with regard to function, functional regulation, involvement in cellular signalling, complex-forming ability, spectrum of binding partners and involvement in the pathophysiology of human diseases are available for SLC41A1. Three recent observations namely the identification of the null mutation, c.698G>T, in SLC41A1 underlying the nephronophthisis-like phenotype, the recognition of a putative link between SLC41A1 and Parkinson's disease, and the observation that nearly 55% of preeclamptic placental samples overexpress SLC41A1, marks the protein as a possible therapeutic target of these diseases. A potential role of the SLC41 family of Mg²⁺ transporters in the pathophysiology of human diseases is further substantiated by the finding that SLC41A3 knockout mice develop abnormal locomotor coordination.