A subgroup of patients with thiazide-induced hyponatremia may carry a variant allele of the prostaglandin transporter SLCO2A1 gene that leads to reduced ability to transport prostaglandin E2 across the apical cell membrane; this reduction of prostaglandin E2 transport leads to increased luminal prostaglandin E2 and activates luminal EP4 receptors, causing membrane trafficking of AQP2 in the absence of AVP, directly reducing urine dilution and free-water excretion (Filippone et al., 2020). Here, AVP is linked to Hyponatremia.