The angiotensin-vasopressin receptor (AVR) responds with equivalent affinities to angiotensinII and vasopressin, and is coupled to adenylate cyclase, hence a V2-type vasopressin-receptor. AVR maps to the Nalp6 locus and overlaps with the larger Nalp6/PYPAF5 reported to be T-cell/granulocyte-specific, cytoplasmic-specific pro-apoptotic protein, thus questioning the existence of AVR. Here we confirm, through different experimental modalities, that AVR is distinct from Nalp6/PYPAF5 based on different mRNA- and protein-sizes, subcellular localization, and tissue-specific expression patterns. Binding studies of PYPAF5-specific Cos1-transfectants detects high-affinity binding to vasopressin but not angiotensinII (AngII), thus assigning PYPAF5 as a non-angiotensin/vasopressin receptor (NAVR). Signaling array analysis reveals that AVP-stimulation of AVR- and NAVR-specific Cos1-transfectants results in diametrical, as well as co-activation of signaling pathways known to mediate renal sodium and water-balance. Likewise, AngII-stimulation of Cos1-AVR reveals a distinct signaling profile from AVP-stimulated Cos1-AVR transfectants. Analysis of genomic organization of AVR/NAVR locus shows an overlapping gene arrangement with alternative promoter usage resulting in different N-termini for NAVR and AVR. In addition to core promoter elements, androgen and estrogen response elements are detected. Promoter analysis of NAVR/AVR 5' regulatory region detects transcriptional upregulation by testosterone and synergistic upregulation by testosterone and estrogen, thus suggesting that AVR and/or NAVR contribute to gender-specific V2-type vasopressin-mediated effects. Altogether, confirmation of AVR and identification of NAVR as vasopressin receptors are concordant with emerging vasopressin functions not attributable to V1a, V1b or V2 receptors, and add molecular bases for multifunctional complexity of vasopressin-mediated functions and regulation.