CNNM3 (cyclin and CBS domain divalent metal cation transport mediator 3) is a magnesium transporter that plays crucial roles in cellular magnesium homeostasis and oncogenesis. The protein functions as a magnesium transporter, with its activity regulated through interactions with phosphatase of regenerating liver (PRL) proteins, particularly PRL-2 1. CNNM3 forms functional heterodimers with PRL-2 through a unique loop in its CBS domain, and this interaction is essential for regulating intracellular magnesium levels and magnesium influx 1. The protein's transport activity is also modulated by ARL15, which promotes complex N-glycosylation of CNNM3 and negatively regulates magnesium uptake 2. CNNM3 has significant disease relevance, particularly in cancer. Low CNNM3 expression is associated with poor prognosis in kidney renal clear cell carcinoma (KIRC), and CNNM3 knockdown promotes cancer cell proliferation and migration while increasing intracellular magnesium and iron levels 3. The protein demonstrates pro-oncogenic properties, with its expression correlating positively with tumor proliferative index in breast cancer 1. Clinically, CNNM3 represents a potential therapeutic target, as disruption of PRL-CNNM3 interactions decreases cancer proliferation, and the protein's role in ferroptosis sensitivity offers new treatment strategies for cancers with low CNNM3 expression 34.