SLC22A17 is a cell surface receptor for lipocalin-2 (LCN2) that functions as a critical iron transporter and regulator of iron homeostasis 1. The protein binds iron-bound LCN2, facilitating its internalization and intracellular iron delivery, which inhibits apoptosis and supports cell survival 2. Conversely, SLC22A17 can mediate iron depletion through association with intracellular siderophores, promoting apoptosis 3. Mechanistically, SLC22A17 interacts with p62 to modulate Nrf2 antioxidant signaling; loss of SLC22A17 impairs iron efflux and triggers iron-catalyzed reactive oxygen species production 4. The receptor also activates JAK2/STAT3 signaling in target cells when engaged by LCN2 5. Dysregulation of SLC22A17 is implicated in multiple pathological contexts: excessive SLC22A17 expression contributes to blood-brain barrier disruption during cerebral ischemia through ferroptosis and tight junction dysfunction 6, while SLC22A17 loss protects cardiomyocytes from doxorubicin toxicity 7. Conversely, SLC22A17 upregulation supports cancer cell survival in iron-restricted microenvironments like the cerebrospinal fluid and brain 25, and elevated LCN2/SLC22A17 signaling suppresses neurogenesis in Alzheimer's disease 3. These findings establish SLC22A17 as a multifunctional iron homeostasis regulator with opposing roles in pathological and adaptive contexts.