The Non-Phototrophic Hypocotyl3 (NPH3)-Root Phototropism2 (RPT2-Like proteins (NRLs), are important for hormone and stress responses yet their cellular functions, particularly the roles of the plant-specific NPH3-domain, remain largely unknown. Several new aspects of NRL function emerged from NRL5 proximity labeling and protein interaction assays. One is that that NRL5 interacts with a number of trafficking-related proteins including SYP132 and SHOU4/SHOU4L, which are involved in exocytic trafficking. These interactions were disrupted by the NRL5P335L mutation which renders the NPH3-domain non-functional. The Q-Snare SYP132, together with its cognate R-SNARE VAMP721/722, which was previously found to interact with NRL5, control the trafficking of plasma membrane proteins such as AHA1/2 and PIP aquaporins, which were also identified in the NRL5 proximity labeling. SYP132 and VAMP721/722 also control the secretion of PR1 and we found that nrl5-1 had ectopic secretion of PR1. We also found extensive hetero-interactions between NRLs which were dependent upon the BTB domain. This suggests a more complex web of NRL complex formation than previously suspected as well as association with PIN auxin transporters. Overall, these data add credence to the proposal that NRL5, and likely other NPH3 domain proteins, are plant-specific component of the intracellular trafficking machinery. NRL5 is part of a web of NRL interactions and has a prominent role in trafficking of stress related proteins including PR1.