Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4)

Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) is a magnesium transporter predominantly expressed in the basolateral membranes of epithelial cells in the intestine and ameloblasts in teeth. It mediates the extrusion of intracellular Mg2+ in exchange for extracellular Na+, playing a central role in systemic magnesium balance and proper enamel formation. CNNM4 includes several structural domains: a transmembrane DUF21 domain, a pair of CBS (cystathionine β-synthase) regulatory domains, and a cyclic nucleotide-binding homology (CNBH) domain, all involved in Mg2+-ATP binding, protein-protein interactions, and cellular localization. Germline mutations of *CNNM4* cause Jalili syndrome—a rare autosomal recessive disorder combining amelogenesis imperfecta and retinal cone-rod dystrophy due to defective magnesium transport in dental and retinal tissues. CNNM4 may also regulate energy metabolism and is inversely linked to tumor progression in some cancer types[1][2][3][5][6]. There are currently no drugs established to directly target CNNM4.

Other names

Metal transporter CNNM4Ancient conserved domain-containing protein 4Cyclin-M4ACDP4SLC70A4KIAA1592Ancient conserved domain protein 4

Not established for any marketed or investigational drugs; CNNM4 primarily mediates Na+/Mg2+ exchange and is indirectly implicated in magnesium homeostasis and possibly tumor biology through energy metabolism.