Cell membrane polyamine/proton antiporter, involved in the detoxification of excess polyamines in the cytoplasm (PubMed:24576949, PubMed:27148215). Involved in the resistance to the imidazole antifungal drugs tioconazole, miconazole, clotrimazole and ketoconazole; to the triazole fluconazole; but not to the antifungals flucytosine or amphotericin B (PubMed:24576949). Plays a role in spermine homeostasis, but spermine accumulation in response to clotrimazole is independent of TPO3 (PubMed:24576949, PubMed:27148215). Expression is up-regulated under spermine stress and depends on the pleiotropic drug resistance transcription factor PDR1 (PubMed:24576949). Increases the susceptibility to the imidazole antifungal drugs tioconazole, miconazole, clotrimazole and ketoconazole; to the triazole fluconazole; but not to the antifungals flucytosine or amphotericin B (PubMed:24576949, PubMed:27148215). Belongs to the major facilitator superfamily. DHA1 family. Polyamines/proton antiporter (TC 2.A.1.2.16) subfamily.