# The SLC41 Family of Magnesium Transporters: Molecular Regulators of Magnesium Homeostasis and Their Multifaceted Roles in Human Diseases **Authors:** Yu Cao, Caijun Rao, Zhipeng Du PMC · DOI: 10.3390/ijms27041673 · International Journal of Molecular Sciences · 2026-02-09 ## TL;DR This review explores the SLC41 family of magnesium transporters and their roles in maintaining magnesium balance and contributing to various diseases. ## Contribution The paper synthesizes current knowledge on SLC41 transporters, highlighting their functions and disease associations for potential therapeutic targeting. ## Key findings - SLC41A1 acts as a Na+/Mg2+ exchanger, a key Mg2+-efflux system. - SLC41A3 facilitates Na+-dependent Mg2+ efflux from mitochondria. - SLC41s are linked to diseases like Parkinson’s and hepatocellular carcinoma. ## Abstract Magnesium ion (Mg2+), particularly its free intracellular form, is indispensable for regulating diverse cellular functions. This critical role implies the existence of dedicated transporters and channels in the plasma membrane that coordinate Mg2+ uptake, intracellular storage, and efflux to maintain homeostasis. Although numerous molecular entities responsible for such Mg2+ transport have been reported over the past decades, there is still limited knowledge of their precise functions and disease implications. This review focuses on the solute carrier family 41 (SLC41), which consists of three isoforms (A1, A2, and A3) that share homology with the prokaryotic magnesium transporter E (MgtE) Mg2+ transporter family. Accumulating evidence has established SLC41A1 as the Na+/Mg2+ exchanger—a predominant Mg2+-efflux system. By contrast, the subcellular site of SLC41A2-mediated Mg2+ flux remains undefined, with potential roles at either the plasma membrane or organellar membranes, and SLC41A3 facilitates Na+-dependent Mg2+ efflux from mitochondria. Additionally, several studies have reported the association between SLC41s and diseases, including Parkinson’s disease, hepatocellular carcinoma, and nephronophthisis-related ciliopathies. By synthesizing current knowledge, this review aims to enhance the understanding of SLC41 transporters in health and disease and to explore their potential as therapeutic targets for clinical intervention. ## Linked entities - **Genes:** SLC41A1 (solute carrier family 41 member 1) [NCBI Gene 254428], SLC41A2 (solute carrier family 41 member 2) [NCBI Gene 84102], SLC41A3 (solute carrier family 41 member 3) [NCBI Gene 54946], SLC4-1 (HCO3 transporter) [NCBI Gene 17281193] - **Chemicals:** Mg2+ (PubChem CID 888), Na+ (PubChem CID 923) - **Diseases:** Parkinson’s disease (MONDO:0005180), hepatocellular carcinoma (MONDO:0007256) ## Full-text entities - **Genes:** Ebp (EBP cholestenol delta-isomerase) [NCBI Gene 13595] {aka Pabp, SI, Td, mSI}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Slc31a2 (solute carrier family 31, member 2) [NCBI Gene 20530] {aka CTR2}, SLC41A2 (solute carrier family 41 member 2) [NCBI Gene 84102] {aka SLC41A1-L1}, TRPM7 (transient receptor potential cation channel subfamily M member 7) [NCBI Gene 54822] {aka ALSPDC, CHAK, CHAK1, LTRPC7, LTrpC-7, TRP-PLIK}, TRPM6 (transient receptor potential cation channel subfamily M member 6) [NCBI Gene 140803] {aka CHAK2, HMGX, HOMG, HOMG1, HSH}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Spint2 (serine protease inhibitor, Kunitz type 2) [NCBI Gene 20733] {aka HAI-2}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, Cdk1 (cyclin dependent kinase 1) [NCBI Gene 12534] {aka Cdc2, Cdc2a, p34}, MAGT1 (magnesium transporter 1) [NCBI Gene 84061] {aka CDG1CC, IAP, MRX95, OST3B, PRO0756, SLC58A1}, Krtcap2 (keratinocyte associated protein 2) [NCBI Gene 66059] {aka 0610010I12Rik, Kcp2}, Yipf6 (Yip1 domain family, member 6) [NCBI Gene 77929] {aka A430107J06Rik}, Ccn2 (cellular communication network factor 2) [NCBI Gene 64032] {aka CTGRP, Ctgf}, Ccl21a (C-C motif chemokine ligand 21 (serine)) [NCBI Gene 18829] {aka 6CKBAC2, 6Ckine, ALP, CKb9, Gm1987, SCYA21a}, MIR522 (microRNA 522) [NCBI Gene 574495] {aka MIRN522, hsa-mir-522, mir-522}, Bcap31 (B cell receptor associated protein 31) [NCBI Gene 27061] {aka Bap31}, Ppib (peptidylprolyl isomerase B) [NCBI Gene 19035] {aka Cphn-2, Cphn2, CyP-20b}, Nfatc4 (nuclear factor of activated T-cells 4) [NCBI Gene 305897] {aka NF-AT3, NF-ATc4}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, Slc41a1 (solute carrier family 41, member 1) [NCBI Gene 98396] {aka B230315F01Rik}, KCNAB2 (potassium voltage-gated channel subfamily A regulatory beta subunit 2) [NCBI Gene 8514] {aka AKR6A5, HKvbeta2, HKvbeta2.1, HKvbeta2.2, KCNA2B, KV-BETA-2}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, SLC41A3 (solute carrier family 41 member 3) [NCBI Gene 54946] {aka SLC41A1-L2}, Tmem147 (transmembrane protein 147) [NCBI Gene 69804] {aka 2010004E11Rik, 5033425B17Rik, Nifie14}, NFATC3 (nuclear factor of activated T cells 3) [NCBI Gene 4775] {aka NF-AT4c, NFAT4, NFATX, n339260}, Slc39a13 (solute carrier family 39 (metal ion transporter), member 13) [NCBI Gene 68427] {aka 1100001L14Rik, ZIP-13, ZIP13}, Camp (cathelicidin antimicrobial peptide) [NCBI Gene 12796] {aka CAP18, CLP, Cnlp, Cramp, FALL39, MCLP}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, slc41a1 (solute carrier family 41 member 1) [NCBI Gene 325975] {aka fd54c09, wu:fd54c09}, MRS2 (magnesium transporter MRS2) [NCBI Gene 57380] {aka HPT, MRS2L}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, SLC41A1 (solute carrier family 41 member 1) [NCBI Gene 254428] {aka MgtE, NPHPL2}, CBS (cystathionine beta-synthase) [NCBI Gene 875] {aka HIP4}, Slc41a1 (solute carrier family 41 member 1) [NCBI Gene 363985], Ier3ip1 (immediate early response 3 interacting protein 1) [NCBI Gene 66191] {aka 1110057H19Rik}, Cdk5 (cyclin dependent kinase 5) [NCBI Gene 12568] {aka Crk6}, CNNM4 (cyclin and CBS domain divalent metal cation transport mediator 4) [NCBI Gene 26504] {aka ACDP4, SLC70A4}, Prkdc (protein kinase, DNA activated, catalytic polypeptide) [NCBI Gene 19090] {aka DNA-PKcs, DNAPDcs, DNAPK, DNPK1, DOXNPH, HYRC1}, CNNM1 (cyclin and CBS domain divalent metal cation transport mediator 1) [NCBI Gene 26507] {aka ACDP1, CLP-1, SLC70A1}, Slc35b1 (solute carrier family 35, member B1) [NCBI Gene 110172] {aka AXER, UGTrel1, Ugalt2}, Nfatc3 (nuclear factor of activated T-cells 3) [NCBI Gene 361400] {aka NFAT4, NFATx}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932] - **Diseases:** preeclampsia (MESH:D011225), NIPA (MESH:D011218), READ (MESH:D012004), TGCT (MESH:C563236), PRAD (MESH:D000230), Non-Tumor Diseases (MESH:D009369), uterine carcinosarcoma (MESH:D002296), developmental abnormalities (MESH:D006130), pancreatic adenocarcinoma (MESH:D010190), stomatocytosis (MESH:C566111), PD (MESH:D010300), injury to (MESH:D014947), Neurodegenerative Disease (MESH:D019636), PDAC (MESH:D021441), ACC (MESH:D003528), cardiac fibrosis (MESH:D005355), GBM (MESH:D005910), LUSC (MESH:D002294), preeclamptic (MESH:C538543), HNSC (MESH:D000077195), adrenocortical carcinoma (MESH:D018268), hypoxia (MESH:D000860), ciliopathies (MESH:D000072661), COAD (MESH:D003110), non- (MESH:C580335), acute myeloid leukemia (MESH:D015470), sarcoma (MESH:D012509), CHOL (MESH:D018281), LUAD (MESH:D000077192), hypoxic (MESH:D002534), STAD (MESH:D013274), Cardiovascular Disease (MESH:D002318), brain lower grade glioma (MESH:C564230), UCEC (MESH:D016889), THCA (MESH:D013964), NPHLP (MESH:C537699), colon cancer (MESH:D015179), dental caries (MESH:D003731), tubular defects (MESH:D015499), KIRC (MESH:D002292), glioblastoma multiforme (MESH:D005909), BLCA (MESH:D001749), PH (MESH:D006976), LIHC (MESH:D006528), DLBC (MESH:D016403), ovarian serous cystadenocarcinoma (MESH:D010049), PCPG (MESH:D010673), ESCA (MESH:D004938), THYM (MESH:D013945), mesothelioma (MESH:D008654), UVM (MESH:C536494), cardiac injury (MESH:D006331), skin cutaneous melanoma (MESH:C562393), respiratory system diseases (MESH:D015619), lymphoid neoplasm (MESH:D008223), degeneration of dopaminergic neurons (MESH:D009410), T2D (MESH:D003924), breast cancer (MESH:D001943), KICH (MESH:D007674) - **Chemicals:** KCN (MESH:D011190), monocrotaline (MESH:D016686), sugars (MESH:D000073893), FCCP (MESH:D002259), nigericin (MESH:D009550), 6-OHDA (MESH:D016627), Cl- (MESH:D002713), HCO3- (MESH:D001639), quinidine (MESH:D011802), MgSO4 (MESH:D008278), K+ (MESH:D011188), Ba2+ (MESH:C080430), imipramine (MESH:D007099), Na+ (MESH:D012964), 6-hydroxyamine (-), DMU-212 (MESH:C482492), Magnesium (MESH:D008274), dopamine (MESH:D004298), ATP (MESH:D000255), isoproterenol (MESH:D007545), Co2+ (MESH:D002245) - **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090], Hepatitis B virus (no rank) [taxon 10407], Salmonella enterica (species) [taxon 28901], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Danio rerio (leopard danio, species) [taxon 7955], Gallus gallus (bantam, species) [taxon 9031], Xenopus laevis (African clawed frog, species) [taxon 8355] - **Mutations:** g.104821402C>T, c.1049C>T, g.126096213G>T, c.436A>G, rs823128, p.G223V, rs1572931, c.1440A>G, rs708727, p.P480P, rs10861279, g.205795512G>A,C, g.205793278C>T, c.698G>T, R244H, g.205810103G>A,C - **Cell lines:** Tom-1 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_XF75), CHOL — Homo sapiens (Human), Cholangiocarcinoma, Cancer cell line (CVCL_4Z42), BV173 — Homo sapiens (Human), Chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0181), MOLT4 — Homo sapiens (Human), Adult T acute lymphoblastic leukemia, Cancer cell line (CVCL_0013), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), Reh — Homo sapiens (Human), Childhood B acute lymphoblastic leukemia, Cancer cell line (CVCL_1650), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), Jurkat — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0065), DT40 — Gallus gallus (Chicken), Chicken bursal lymphoma, Cancer cell line (CVCL_0249), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12941325/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941325/full.md ## References 76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941325/full.md --- Source: https://tomesphere.com/paper/PMC12941325