The regulated release of peptide hormones depends on their packaging into dense-core vesicles (DCVs). Two models have been proposed for DCV cargo sorting. The "sorting by entry" model proposes that DCV cargos selectively enter nascent DCVs at the trans-Golgi network (TGN). The "sorting by exit" model proposes that sorting occurs by the post-TGN removal of non-DCV cargos and retention of mature DCV cargos. Here we show that the coiled-coil protein CCDC186 controls sorting by exit. Ccdc186 KO insulinoma cells secrete less insulin, fail to retain insulin and carboxypeptidase E in mature DCVs at the cell periphery, and fail to remove carboxypeptidase D from immature DCVs. A mutation affecting the endosome-associated recycling protein (EARP) complex causes similar defects in DCV cargo retention and removal.CCDC186 and EARP may act together to control the post-Golgi retention of cargos in mature DCVs.cargos in mature DCVs in axons, but it is unclear how RAB-2 and CCCP-1/CCDC186 are connected to EARP. In both C. elegans and in the rat insulinoma 832/13 cell line, RAB-2 and CCCP-1/CCDC186 colocalize near the TGN where the early steps of DCV biogenesis take place (Ailion et al., 2014; Cattin-Ortolá et al., 2017). EARP is localized to two distinct compartments in 832/13 cells, a recycling endosome compartment and a compartment near the TGN where it colocalizes with CCDC186 (Topalidou, Cattin-Ortolá, et al., 2018). Additionally, Eipr1 knockout 832/13 cells have reduced insulin secretion and an altered distribution of insulin in the cell, with relatively more insulin near the TGN and less at the cell periphery (Topalidou, Cattin-Ortolá, et al., 2018). Thus, EARP and EIPR1 may be important for acting near the TGN to ensure the retention of processed cargos in mature DCVs.Here we investigate the role of CCDC186 in DCV biogenesis, maturation, and cargo sorting in 832/13 cells. Our results suggest that CCDC186 acts together with EARP to control several aspects of DCV cargo sorting, including the post-Golgi removal of some non-DCV cargos and retention of mature DCV cargos.